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text:
Ratings based on 619 Verified Reviews
They paid and stayed. We double-checked.
3.0 Room cleanliness
3.1 Service & staff
3.0 Room comfort
2.6 Hotel condition
Expedia Verified ReviewsThey paid and stayed. We double-checked.
by A verified traveler from Baton Rouge, LA
24 hoursPosted May 28, 2016
Went to the N.O. Saints softball that was being played in the city of New Orleans. Needed a place to stay for 24 hrs. We have stay here before. No problem staying. Quick breakfast. Nice overall. I would stay again.
by A verified traveler from EC
Near to convention centerPosted May 15, 2016
Good location near to the convention center 10 minutes by car. Poor cleanings of the room and the pool imposible to use .
by A verified traveler from Texas
Not yet renovated "no tell motel"Posted May 3, 2016
Pros: The lobby is GORGEOUS but don't go any further or you will be disappointed (Knight's Inn signs remain on most of the property).
Cons: Everything except the lobby.
Location: Location is exceptional. Close to convention center, close to cruise port, close (not walking distance) to downtown.
Check-in took 45 minutes because clerk could not get any computers to work (but the other clerk was checking in multiple people on same computers within that same 45 minutes). Third floor room; elevator out of order. "Free WiFi" out of order for entire stay. A/C had two settings: off and "meat locker". Water leak in wall near sink equals wet carpet and stench. Booked for 3 people; amenities set up for 2 people and requests for additional towels etc generated dirty looks. Trashcans in walkways overflowing and not emptied even once during our stay. Walkways just downright dirty. Pool was green. I would call this hotel "barely sleepable". Drive one more mile and stay at LaQuinta...I don't know if it is any better, but couldn't be any worse and price is very close.
by A verified traveler
Good place for the pricePosted Apr 30, 2016
Stayed 2 days for Jazz fest. Cheap price, good location. $14 uber drive to jazz fest, $12 to Bourbon street.
by A verified traveler
Posted Apr 27, 2016
Not bad for the price and location! I would recommend not eating anything from the hotel. Microwave slop that was horrible
by A verified traveler from California
Horrible customer servicePosted Apr 25, 2016
Pros: Nothing not even the breakfast was good
Cons: Everything especially the customer service
Location: There is a walmart a cross the street and some eating places that are a half mile or shorter a way.
The hotel staff had poor customer service. Upon checking in I waited in line over an hour to get checked in and only one person was in front of me. The front desk lady said it was because of the key card machine being down but don't they have a master key, so that we could at least get in our room after flying 6 hours. When I asked to speak to the manager, the manager was awful she was worst than the front desk lady. She walked away from me before I finished explaining my issue. Finally when they said we could check in, the lady takes another customer before me and I had been waiting for an hour. Finally when I got to check in, guess what? My room key was already made and I could have been in my room. When I got to my room, it was okay until I saw that there was no smoke alarm. You can see where the frame for the smoke detector was but no fire detector was on it. The bathroom walls were rusted and the bathtub drain didn't have a cover on it. The "buffet" breakfast was awful. They only had scrambled eggs and oatmeal. Plus cereal and over cooked make your own waffles. My mother asked the lady in the kitchen was that all the food and the lady said a nasty remark, saying "what you see is what you get." There are other things that went wrong but I am unable to fit them in this document.
by A verified traveler from Washington state
Nothing special.Posted Apr 11, 2016
Smoke alarm in room was broken, the face was off and no battery. Not very safe, especially on 2ND floor. Doors locked to breakfast room, had to go all the way to lobby to get in. Not much put out for breakfast. More on Sat than on previous 2 days.
by A verified traveler from n'awlins
Not quite surePosted Apr 5, 2016
The main entrance was really nice, the property was OK, pool was eww but it's the end of winter so you get a pass, the room was OK, just seemed like something should have been wrong, not quite sure how I feel. For the price and 1 night, not bad
by A verified traveler from ok
horriblePosted Mar 21, 2016
Terrible hotel! Room was dirty. Soiders in the bed, hair in the bathroom floor and a tv that didn't work. When we called the front desk they said sorry we don't have s technician working and if you need more towels you will have to come get them we only have 2 people working. I can't say enough about how bad this hotel stay was, we will never stay days inn again
by A verified traveler from New Orleans, LA
The Days Inn Gretna was adequate for the pricePosted Mar 18, 2016
If you're looking for a cheap room for a quick stay and don't mind seeing a pool shut down, ice machine broken and missing towels than stay at the Days Inn Gretna. The Staff were great and breakfast was good. So, it was adequate at $65 a night.


text:
MLC elections: Parties rack brains to select candidatesWith just four days left for filing nominations for the Legislative Council elections, the Congress, BJP and JD(S) were busy finalising their candidates and strategies on Friday for the polls scheduled to be held on June 10. Elections will be held for seven ... Deccan Herald, 1 day ago
Golkar party to support government post-congress: ARB
Nusa Dua (ANTARA News) - Chairman of Golkar Aburizal Bakrie (ARB) has reiterated that the party will support the President Joko Widodo (Jokowi) and Vice President M. Jusuf Kalla (JK) administration after the extraordinary congress. "Later, in this ...Antara News, 2 weeks ago
Pradeep Shetty is New Sirsi CMC President
Sirsi: Congress rebel Pradeep Shetty has been elected president of the Sirsi City Municipal Council. Aruna Vernekar was chosen vice-president for the second term. The election held on Wednesday held suspense till the eleventh hour. Congress member ...SahiOnline, 1 month ago Yadgir CMC gets new president, V-P The Hindu, 2 months ago
YSRCP hunger strike enters fourth day
: The indefinite hunger strike launched by the YSR Congress Party (YSRCP), demanding a separate Railway Zone at this Port city headquarters for Andhra Pradesh, entered the Fourth day today. The indefinite fast observed by YSR Congress Party's ...NetIndia123.com, 1 month ago
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Gajula Jayalalita and Benakal Basavaraj were elected unopposed as Mayor and Deputy Mayor of the Congress-controlled Ballari City Corporation here on Monday. Amlan Aditya Biswas, Regional Commissioner, who conducted the election proceedings ...The Hindu, 2 months ago
President Jokowi and 11 other leaders attend ASEAN-Russia Summit
Sochi, Russia (ANTARA News) - President Joko Widodo (Jokowi) and other ASEAN leaders are expected to attend the ASEAN-Russia Summit hosted by Russian President Vladimir Putin. "The commemoration of the 20th anniversary of the cooperation between ...Antara News, 1 week ago
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What do ya know, we went to another Open Mic. Thursday was a particularly huge night for the 40+ crowd. Just because you have kids doesn't mean you can't have a second music career once your kids graduate. Open Mic is calling.
Tonight we made the rookie mistake of showing up at 9:00. The trick is, if you really wanna have a good time – don't show too early. Just don't do it. The hour between nine and ten is limbo at the Alaskan. You could just as easily walk out as you could order a beer. It's a fine line between what am I doing with my life back at the Alaskan, on Thursday, again, and I've had a rough week. Thursday's the new Friday. I really wanna wear this new tunic top. I deserve this.
But you're not gonna walk because this is Open Mic, and you're about to have a really, really great time (after two beers.)
Chad helped sweeten the pot with a round of free beers for the ladies.
Brian kicked off Open Mic for the night beginning his set with the Dr. Hook song Sylvia's Mother. Without fail this guys opens every Open Mic at the Alaskan with the same songs. Sometimes electric, sometimes acoustic, and sometimes with his parrot named Winter (this guy actually has a parrot.) Before ending his set he claimed, "I know more cover songs than the Grateful Dead!" We believe him. That beard has stories…
You won't catch these cool cats having a bad time. Giono, Kaley and Travis keeping it real in the back section.
They call him the general manager, but we all know he's king of Open Mic. C. Scott Fry is one bad mother on the guitar. If you like what you hear, there's always more country blues songs on his radio show, Fry's the Limit, from 3-5 on Saturday. What else would you listen to when you drop off your recycling? Duh.
And lucky us! A harmonica player hopped onstage. This guy gave Scott a run for his money.
The James Radio Hour was having a good time too. Remember when the Flaming Lips played the Gorge in '93? We don't, but James does better than anyone. He has every one of their live albums, making his show the perfect pre-game to Open Mic Thursdays from 7 to 9. Don't miss it.
Open Mic may have been a man's world last Thursday, but when Teri Tibbett got onstage she was the queen. This lady is Open Mic Royalty, and we suspect she's been playing the Alaskan since the late '80s. Teri's a pro. Also fun fact: She has Ferrets. Which made us think of this story.
Maybe you've heard these guys on the radio? Here's DJ Taco Todd and Kit, KTOO superstars. Todd is one-half of Alaskan Scorcher who will be taking over the Alaskan this weekend for a ska, rocksteady and soul music party on Valentine's Day reminding you that love is all about the fire.
We can't wait to get older because we know we will soon be able to afford sweet instruments like this guy's guitar which sounded really expensive. We watched him tune it for a half hour. Did we mention his deep voice? Like a fine wine, it was aged to perfection.
And then there's Joe Emerson. He's quiet and understated, but easily the best guitarist in the bar.
And.. then there's the bar close, single guy round-up. They'll be back tonight ladies, will you?
Find Jessie on Instagram @messyjessiehh and Annie at @annibalaska
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text:
Special Issue Paper
Trust dynamic task allocation algorithm with Nash equilibrium for heterogeneous wireless sensor network
Version of Record online: 7 MAY 2014
DOI: 10.1002/sec.1026
Copyright © 2014 John Wiley & Sons, Ltd.
Security and Communication Networks
Special Issue: Security, trust, and resilience of distributed networks and systems
Volume 8, Issue 10, pages 1865–1877, 10 July 2015
Additional Information
How to Cite
2015), Trust dynamic task allocation algorithm with Nash equilibrium for heterogeneous wireless sensor network. Security Comm. Networks, 8, 1865–1877. doi: 10.1002/sec.1026., , , and (
Publication History
- Issue online: 19 MAY 2015
- Version of Record online: 7 MAY 2014
- Manuscript Accepted: 24 MAR 2014
- Manuscript Revised: 28 FEB 2014
- Manuscript Received: 30 AUG 2013
- Abstract
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Detection of BK virus DNA in nasopharyngeal aspirates from children with respiratory infections but not in saliva from immunodeficient and immunocompetent adult patients.
Sundsfjord, A
Spein, A R
Lucht, E
Flaegstad, T
Seternes, O M
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Our understanding of important stages in the pathogenesis of the human polyomavirus BK virus (BKV) and JC virus (JCV) infections is limited. In this context, nasopharyngeal aspirates from 201 children with respiratory diseases and saliva from 60 human immunodeficiency virus type 1-infected adults and 10 healthy adult controls were collected and analyzed for the presence of BKV and JCV DNA by PCR. Neither BKV nor JCV DNA was detected in the saliva specimens. We demonstrated BKV DNA, but no infectious BKV, in 2 of 201 nasopharyngeal aspirates. Each sample contained one unique rearranged noncoding control region variant of BKV. The results indicate that (i) BKV and JCV are not regularly associated with respiratory infections in children requiring hospitalization, (ii) nasopharyngeal cells are not an important site for primary replication of human polyomavirus BKV and JCV, and (iii) the salivary glands and oropharyngeal cells seem not to be involved in BKV and JCV persistence. We propose that for the polyomaviruses BKV and JCV the alimentary tract should be considered as a portal of entrance to the human organism.
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BK polyomavirus (BKPyV) is the most common viral pathogen among allograft patients. Increasing evidence links BKPyV to the human oral compartment and to HIV-associated salivary gland disease (HIVSGD). To date, few studies have analyzed orally derived BKPyV. This study aimed to characterize BKPyV isolated from throat wash (TW) samples from HIVSGD patients. The replication potential of HIVSGD-derived clinical isolates HIVSGD-1 and HIVSGD-2, both containing the noncoding control region (NCCR) architecture OPQPQQS, were assessed and compared to urine-derived virus. The BKPyV isolates displayed significant variation in replication potential. Whole-genome alignment of the two isolates revealed three nucleotide differences that were analyzed for a potential effect on the viral life cycle. Analysis revealed a negligible difference in NCCR promoter activity despite sequence variation and emphasized the importance of functional T antigen (Tag) for efficient replication. HIVSGD-1 encoded full-length Tag, underwent productive infection in both human salivary gland cells and kidney cells, and expressed viral DNA and Tag protein. Additionally, HIVSGD-1 generated DNase-resistant particles and by far surpassed the replication potential of the kidney-derived isolate in HSG cells. HIVSGD-2 encoded a truncated form of Tag and replicated much less efficiently. Quantitation of infectious virus, via the fluorescent forming unit assay, suggested that HIVSGD BKPyV had preferential tropism for salivary gland cells over kidney cells. Similarly, the results suggested that kidney-derived virus had preferential tropism for kidney cells over salivary gland cells. Evidence of HIVSGD-derived BKPyV oral tropism and adept viral replication in human salivary gland cells corroborated the potential link between HIVSGD pathogenesis and BKPyV.
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Buruli ulcer is a severe human skin disease caused by Mycobacterium ulcerans. This disease is primarily diagnosed in West Africa with increasing incidence. Antimycobacterial drug therapy is relatively effective during the preulcerative stage of the disease, but surgical excision of lesions with skin grafting is often the ultimate treatment. The mode of transmission of this Mycobacterium species remains a matter of debate, and relevant interventions to prevent this disease lack (i) the proper understanding of the M. ulcerans life history traits in its natural aquatic ecosystem and (ii) immune signatures that could be correlates of protection. We previously set up a laboratory ecosystem with predatory aquatic insects of the family Naucoridae and laboratory mice and showed that (i) M. ulcerans-carrying aquatic insects can transmit the mycobacterium through bites and (ii) that their salivary glands are the only tissues hosting replicative M. ulcerans. Further investigation in natural settings revealed that 5%–10% of these aquatic insects captured in endemic areas have M. ulcerans–loaded salivary glands. In search of novel epidemiological features we noticed that individuals working close to aquatic environments inhabited by insect predators were less prone to developing Buruli ulcers than their relatives. Thus we set out to investigate whether those individuals might display any immune signatures of exposure to M. ulcerans-free insect predator bites, and whether those could correlate with protection.
Methods and Findings
We took a two-pronged approach in this study, first investigating whether the insect bites are protective in a mouse model, and subsequently looking for possibly protective immune signatures in humans. We found that, in contrast to control BALB/c mice, BALB/c mice exposed to Naucoris aquatic insect bites or sensitized to Naucoris salivary gland homogenates (SGHs) displayed no lesion at the site of inoculation of M. ulcerans coated with Naucoris SGH components. Then using human serum samples collected in a Buruli ulcer–endemic area (in the Republic of Benin, West Africa), we assayed sera collected from either ulcer-free individuals or patients with Buruli ulcers for the titre of IgGs that bind to insect predator SGH, focusing on those molecules otherwise shown to be retained by M. ulcerans colonies. IgG titres were lower in the Buruli ulcer patient group than in the ulcer-free group.
These data will help structure future investigations in Buruli ulcer–endemic areas, providing a rationale for research into human immune signatures of exposure to predatory aquatic insects, with special attention to those insect saliva molecules that bind to M. ulcerans.
Saliva from aquatic insects in areas where Buruli ulcer is endemic can protect mice against the disease's characteristic skin lesion and might play a role in natural immunity in humans.
Editors' Summary
Buruli ulcer disease is a severe skin infection caused by Mycobacterium ulcerans, a bacterium related to those that cause tuberculosis and leprosy. This poorly understood disease affects people living near slow-flowing or standing water in poor rural communities in tropical and subtropical countries. How people become infected with M. ulcerans is unclear but one possibility is that infected aquatic insects transmit it through their bites. The first sign of infection is usually a small painless swelling in the skin. Bacteria inside these swellings produce a toxin that damages nearby soft tissues until eventually the skin sloughs off to leave a large open sore. This usually heals but the resultant scar can limit limb movement. Consequently, 25% of people affected by Buruli ulcers—most of whom are children—are permanently disabled. If the disease is caught early, powerful antibiotics can prevent ulcer formation. But most patients do not seek help until the later stages when the only treatment is to cut out the infection and do a skin graft, a costly and lengthy treatment.
Why Was This Study Done?
There is currently no effective way to prevent Buruli ulcers. To develop an effective preventative strategy, researchers need to determine exactly how the infection is transmitted to people and what makes some individuals resistant to infection. Previous studies have indicated that 5%–10% of some aquatic insect predators that live in areas where Buruli ulcers occur have M. ulcerans in their salivary glands and that aquatic insects carrying M. ulcerans can transmit it to mice through bites. Furthermore, people working close to water inhabited by insect predators are less likely to develop Buruli ulcers than their relatives who do not work near water. In this study, therefore, the researchers investigated whether exposure to noninfected insect saliva provides some protection against M. ulcerans infection.
What Did the Researchers Do and Find?
The researchers let uninfected aquatic insects bite ten mice several times before exposing these mice and ten unbitten mice to M. ulcerans-infected water bugs. Only one pre-bitten mouse developed an M. ulcerans-containing lesion compared with eight control mice. Next, the researchers injected mice with insect salivary gland extracts before challenging them with "naked" M. ulcerans or bacteria coated with salivary gland extract. Most uninjected mice developed lesions when challenged with coated or naked M. ulcerans, as did experimental mice challenged with naked M. ulcerans. However, most experimental mice challenged with coated M. ulcerans remained lesion-free. In both experiments, the blood of the pre-bitten and extract-treated mice (but not the control mice) contained antibodies (immune system proteins that provide protection against infections and foreign proteins) to proteins in insect salivary gland extracts that stick to M. ulcerans. Finally, the researchers measured the blood concentration (the titer) of antibodies that bind insect salivary gland proteins in patients with Buruli ulcer and in healthy people living in the same area. People with high titers of these antibodies, they report, were less likely to have Buruli ulcers than those with low titers.
What Do These Findings Mean?
These findings suggest that exposure to aquatic insect saliva may provide some protection against M. ulcerans lesion development. However, the current results have several limitations. In particular they will only be relevant to human disease if M. ulcerans is normally transmitted by insect bites, and this has not been proven yet. Also, because the human study did not measure the overall immune status of the study participants, the people with Buruli ulcers may have had a general immune deficit rather than simply lacking antibodies against insect salivary gland proteins. However, if the human findings can be repeated and expanded, they suggest that low antibody titers to salivary gland proteins might identify those people who are most susceptible to M ulcerans infections and who would thus benefit most from regular tests for early signs of the disease. Finally, further work on the immune mechanism by which exposure to insect salivary gland proteins protects against M. ulcerans infections may help in the development of vaccines against Buruli ulcer disease.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0040064.
A related PLoS Medicine Perspective article by Manuel T. Silva and others discusses this study and others on insect-borne parasitic diseases
World Health Organization has information on Buruli ulcer disease
US Centers for Disease Control and Prevention has information on Buruli ulcer
The US Armed Forces Institute of Pathology Web site contains pages on Buruli ulcer
Leprosy Relief Emmaus Switzerland offers information on Buruli ulcer
Wikipedia contains pages on Buruli ulcer (note: Wikipedia is an online encyclopedia that anyone can edit)
PLoS Medicine has a detailed review article on Buruli ulcer by Paul D. R. Johnson and colleagues
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Entezami, Pouya
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BK virus (BKV) is a human pathogen that causes severe diseases, including polyomavirus-associated nephropathy in kidney transplant patients and hemorrhagic cystitis in bone marrow transplant recipients. How BKV replication is regulated and the effects of a lytic BKV infection on host cells at the molecular level are not well understood. Currently, there is no specific antiviral treatment for BKV-associated disease, and a better understanding of the complete life cycle of the virus is necessary. Here, we report the interplay between BKV and one of the regulatory structures in the host cell nucleus, promyelocytic leukemia nuclear bodies (PML-NBs). Our results show that BKV infection reorganizes PML-NBs as a strategy to inactivate the negative functions of PML-NBs.
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Brennan, Daniel C.
Çuburu, Nicolas
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Viscidi, Raphael P.
Randhawa, Parmjeet S.
Buck, Christopher B.
PLoS Pathogens
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Author Summary
Serological studies have shown that nearly all humans are chronically infected with BK polyomavirus (BKV). The infection isn't usually associated with noticeable symptoms. However, opportunistic replication of BKV in therapeutically immunosuppressed kidney transplant recipients (KTRs) can lead to dysfunction or loss of the engrafted kidney. BKV associated nephropathy can occur even in KTRs with high levels of anti-BKV antibodies that might be expected to neutralize the virus. In this report we provide a possible explanation: we show there are at least two BKV genotypes, which are distinct serotypes with respect to antibody-mediated neutralization. Using a novel neutralization-based approach, we found that about half of 108 KTRs did not have detectable levels of antibodies capable of neutralizing BKV genotype IV (BKV-IV) at the time of transplantation. Of these initially BKV-IV naïve KTRs, about half experienced acute BKV-IV specific seroconversion during the first year after transplantation. This likely reflects a de novo BKV-IV infection arising from the engrafted kidney. In a pilot study, we show that recombinant BKV-IV VLPs can induce high levels of BKV-IV-neutralizing antibodies in vaccinated animals. Our results suggest that administration of a BKV VLP-based vaccine to prospective KTRs might protect against the development of opportunistic BKV replication.
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Bahn, Arthur N.
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Bobbey, Adam
Shen, Daniel H.
Nagy, Rebecca S.
Wakely, Paul E.
Lehman, Amy
Jarjoura, David
Jhiang, Sissy M.
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Oliveira, Fabiano
Lawyer, Phillip G.
Kamhawi, Shaden
Valenzuela, Jesus G.
PLoS Neglected Tropical Diseases
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Methodology/Principal Findings
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Immunization with two salivary proteins from P. papatasi, PpSP15 and PpSP44, produced distinct immune profiles that correlated with resistance or susceptibility to Leishmania infection. The demonstration for the first time that immunity to a defined salivary protein (PpSP44) results in disease enhancement stresses the importance of the proper selection of vector-based vaccine candidates.
Author Summary
In vector-borne diseases, the role of vectors has been overlooked in the search for vaccines. Nonetheless, there is a body of evidence showing the importance of salivary proteins of vectors in pathogen transmission. Leishmaniasis is a neglected vector-borne disease transmitted by sand flies. Pre-exposure to sand fly saliva or immunization with a salivary protein protected mice against cutaneous leishmaniasis. Using DNA immunization we investigated the immune response induced by abundant proteins within the saliva of the sand fly Phlebotomus papatasi. We found that one salivary protein protected while another exacerbated L. major infection, suggesting that the type of immune response induced by specific salivary proteins can prime and direct anti-Leishmania immunity. This stresses the importance of the proper selection of vector-based vaccine candidates. This work validates the powerful protection that can be acquired through vaccination with the appropriate salivary molecule and more importantly, shows that this protective immune response is efficiently recalled by sand fly bites, the natural route of transmission.
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Abreo, Fleurette
Caldito, Gloria
Klein, Ronald L.
Sunavala-Dossabhoy, Gulshan
Human Gene Therapy
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Human Cell
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Virus research
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BK virus; subtype; BC loop; subtyping region
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White, M. R.
Helmerhorst, E. J.
Ligtenberg, A.
Karpel, M.
Tecle, T.
Siqueira, W. L.
Oppenheim, F. G.
Hartshorn, K. L.
Oral microbiology and immunology
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Nandula, Seshagiri Rao
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Scindia, Yogesh M
Bagavant., Harini
Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology
Recent studies have demonstrated the expression of Toll-like receptor 3 (TLR3) in salivary glands and epithelial cell lines derived from Sjögren's syndrome (SS) patients. Since viral infections are considered to be a trigger for SS, in this study we investigated whether in vivo engagement of TLR3 affects salivary gland function.
Female NZB/WF1 mice were repeatedly injected with polyinosinic:polycytidylic acid (poly(I:C)). TLR3 expression within submandibular glands was studied by immunohistochemistry. RNA levels of inflammatory cytokines in the submandibular glands were determined by real time PCR. Pilocarpine induced saliva volume was used as an index of glandular function.
Immunohistochemical analysis of submandibular glands showed TLR3 expression in epithelium of serous and mucous acini, granular convoluted tubules and ducts. Poly(I:C) treatment rapidly upregulated the mRNA levels of type I IFN and inflammatory cytokines in the submandibular glands. By one week after treatment, the saliva volumes in poly(I:C) treated mice were significantly reduced in comparison with the PBS treated mice. Hematoxylin and eosin staining showed that salivary gland histology was normal and lymphocytic foci were not detected. Glandular function recovered after poly(I:C) treatment was stopped.
Our results demonstrate that engagement of TLR3 within the salivary glands results in a rapid loss of glandular function. This phenomenon is associated with the production of type I IFN and inflammatory cytokines in the salivary glands. Restoration of glandular function suggests that for viral etiology of SS, a chronic infection of salivary glands might be necessary.
Inflammatory Cytokines; Poly(I:C); Salivary Gland; Sjögren's Syndrome TLR3
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Xiao, Jianqiao
Tong, Tuong
Zhan, Xiaoyan
Haghjoo, Erik
Liu, Fenyong
Journal of Virology
We have recently generated a pool of murine cytomegalovirus (MCMV) mutants by using a Tn3-based transposon mutagenesis approach. In this study, one of the MCMV mutants, RvM43, which contained the transposon inserted in open reading frame M43, was characterized. Our results provide the first direct evidence to suggest that M43 is not essential for viral replication in vitro in NIH 3T3 cells. Moreover, RvM43 exhibited a titer similar to that of the wild-type virus in the lungs, livers, spleens, and kidneys of both BALB/c and SCID mice and was as virulent as the wild-type virus in killing SCID mice that had been intraperitoneally infected with the viruses. In contrast, titers of the mutant virus in the salivary glands of the infected animals at 21 days postinfection were significantly (100 to 1,000-fold) lower than those of the wild-type virus and a rescued virus that restored the M43 region and its expression. Thus, M43 appears to be not essential for viral growth in vivo in the lungs, livers, spleens, and kidneys of infected animals and is also dispensable for virulence in killing SCID mice. Moreover, our results suggest that M43 is an MCMV determinant for growth in the salivary glands. Studies of viral genes required for replication in the salivary glands are important in understanding the mechanism of viral tropism for the salivary glands and shedding in saliva, which is believed to be one of the major routes of CMV transmission among healthy human populations.
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Le Coupanec, Alain
Babin, Divya
Fiette, Laurence
Jouvion, Grégory
Ave, Patrick
Misse, Dorothee
Bouloy, Michèle
Choumet, Valerie
PLoS Neglected Tropical Diseases
Rift Valley fever (RVF) is a severe mosquito-borne disease affecting humans and domestic ruminants. Mosquito saliva contains compounds that counteract the hemostatic, inflammatory, and immune responses of the host. Modulation of these defensive responses may facilitate virus infection. Indeed, Aedes mosquito saliva played a crucial role in the vector's capacity to effectively transfer arboviruses such as the Cache Valley and West Nile viruses. The role of mosquito saliva in the transmission of Rift Valley fever virus (RVFV) has not been investigated.
Using a murine model, we explored the potential for mosquitoes to impact the course of RVF disease by determining whether differences in pathogenesis occurred in the presence or absence of mosquito saliva and salivary gland extract.
C57BL/6NRJ male mice were infected with the ZH548 strain of RVFV via intraperitoneal or intradermal route, or via bites from RVFV-exposed mosquitoes. The virus titers in mosquitoes and mouse organs were determined by plaque assays.
After intraperitoneal injection, RVFV infection primarily resulted in liver damage. In contrast, RVFV infection via intradermal injection caused both liver and neurological symptoms and this route best mimicked the natural infection by mosquitoes. Co-injections of RVFV with salivary gland extract or saliva via intradermal route increased the mortality rates of mice, as well as the virus titers measured in several organs and in the blood. Furthermore, the blood cell counts of infected mice were altered compared to those of uninfected mice.
Different routes of infection determine the pattern in which the virus spreads and the organs it targets. Aedes saliva significantly increases the pathogenicity of RVFV.
Author Summary
Rift Valley fever is an endemic and epidemic zoonosis in Africa and the Arabic Peninsula. In humans, in the most severe cases the viral infection causes fulminant hepatitis associated with haemorrhagic fever, permanent blindness or severe encephalitis. Despite the importance of vector transmission in the spread of arboviruses, few studies on the physiopathology of viral infection have considered the role of the arthropod in the efficiency of viral infection. Moreover, the route of virus inoculation and the presence of the vector's saliva can potentially affect virus pathogenicity. Our results show that saliva from Aedes mosquitoes increases Rift Valley fever pathogenicity. Importantly, our study also revealed that RVFV transmitted via mosquito bites spread differently than virus inoculated by other routes. These observations may have interesting repercussions given the role mosquitoes were shown to play in the transmission of RVFV in humans during the last outbreak of the disease in Saudi Arabia. Identification of salivary proteins able to increase RVFV virulence may pave the way to new approaches to prevent or cure the disease.
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Transforming growth factor-beta-mediated regulation of BK virus gene expression
Abend, Johanna R.
Imperiale, Michael J.
The increasing prevalence of BK virus (BKV)-associated diseases in immunosuppressed patients has prompted an investigation of the immune response to BKV, especially the role of cytokines in regulating viral replication. We examined the effect of TGF-β, a cytokine that is stimulated by certain immunosuppressive therapies, on BKV gene expression during lytic infection of renal proximal tubule epithelial cells. Viral gene expression, and specifically the activity of the BKV early promoter, is regulated by TGF-β in a strain-dependent manner. Promoter activity is upregulated in the presence of TGF-β for the TU strain of BKV, and not for the Dik, Dunlop, or Proto-2 strains. Using site-directed mutagenesis, we have identified a small segment of the TU promoter that is required for stimulation in response to TGF-β. These results demonstrate that BKV strains can respond differently to cytokine treatment and suggest that TGF-β may play a role in the reactivation of BKV.
polyomavirus; BK virus; TGF-β; Smad3
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The Native Wolbachia Symbionts Limit Transmission of Dengue Virus in Aedes albopictus
Mousson, Laurence
Zouache, Karima
Arias-Goeta, Camilo
Raquin, Vincent
Mavingui, Patrick
Failloux, Anna-Bella
PLoS Neglected Tropical Diseases
The chikungunya (CHIK) outbreak that struck La Reunion Island in 2005 was preceded by few human cases of Dengue (DEN), but which surprisingly did not lead to an epidemic as might have been expected in a non-immune population. Both arboviral diseases are transmitted to humans by two main mosquito species, Aedes aegypti and Aedes albopictus. In the absence of the former, Ae. albopictus was the only species responsible for viral transmission on La Reunion Island. This mosquito is naturally super-infected with two Wolbachia strains, wAlbA and wAlbB. While Wolbachia does not affect replication of CHIK virus (CHIKV) in Ae. albopictus, a similar effect was not observed with DEN virus (DENV).
Methods/Principal Findings
To understand the weak vectorial status of Ae. albopictus towards DENV, we used experimental oral infections of mosquitoes from La Reunion Island to characterize the impact of Wolbachia on DENV infection. Viral loads and Wolbachia densities were measured by quantitative PCR in different organs of Ae. albopictus where DENV replication takes place after ingestion. We found that: (i) Wolbachia does not affect viral replication, (ii) Wolbachia restricts viral density in salivary glands, and (iii) Wolbachia limits transmission of DENV, as infectious viral particles were only detected in the saliva of Wolbachia-uninfected Ae. albopictus, 14 days after the infectious blood-meal.
We show that Wolbachia does not affect the replication of DENV in Ae. albopictus. However, Wolbachia is able to reduce viral infection of salivary glands and limit transmission, suggesting a role of Wolbachia in naturally restricting the transmission of DENV in Ae. albopictus from La Reunion Island. The extension of this conclusion to other Ae. albopictus populations should be investigated.
Author Summary
Aedes albopictus is an invasive species that is expanding its natural range of geographic distribution. While it was previously considered a secondary vector of different arboviruses, this mosquito species is involved in the most recent outbreaks of chikungunya but contributes weakly to dengue outbreaks. Ae. albopictus naturally carries two strains of the bacterium Wolbachia, wAlbA and wAlbB. Present in 20% of insect species, Wolbachia is an obligate intracellular symbiont mainly transmitted through females. When inoculated into some mosquito hosts, Wolbachia is able to shorten the adult life span and to block arbovirus transmission. We have previously shown that Wolbachia is not capable of limiting chikungunya replication in the mosquito vector. In this study, we show that the native Wolbachia is able to limit dengue transmission by restricting the delivery of infectious viral particles from the mosquito saliva when biting. Therefore, our results might explain the low vector competence of Ae. albopictus for dengue, and thus its weak contribution as an epidemic dengue vector.
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BK Polyomavirus Genotypes Represent Distinct Serotypes with Distinct Entry Tropism
Pastrana, Diana V.
Ray, Upasana
Magaldi, Thomas G.
Schowalter, Rachel M.
Çuburu, Nicolas
Buck, Christopher B.
Journal of Virology
BK polyomavirus (BKV) causes significant urinary tract pathogenesis in immunosuppressed individuals, including kidney and bone marrow transplant recipients. It is currently unclear whether BKV-neutralizing antibodies can moderate or prevent BKV disease. We developed reporter pseudoviruses based on seven divergent BKV isolates and performed neutralization assays on sera from healthy human subjects. The results demonstrate that BKV genotypes I, II, III, and IV are fully distinct serotypes. While nearly all healthy subjects had BKV genotype I-neutralizing antibodies, a majority of subjects did not detectably neutralize genotype III or IV. Surprisingly, BKV subgenotypes Ib1 and Ib2 can behave as fully distinct serotypes. This difference is governed by as few as two residues adjacent to the cellular glycan receptor-binding site on the virion surface. Serological analysis of mice given virus-like particle (VLP)-based BKV vaccines confirmed these findings. Mice administered a multivalent VLP vaccine showed high-titer serum antibody responses that potently cross-neutralized all tested BKV genotypes. Interestingly, each of the neutralization serotypes bound a distinct spectrum of cell surface receptors, suggesting a possible connection between escape from recognition by neutralizing antibodies and cellular attachment mechanisms. The finding implies that different BKV genotypes have different cellular tropisms and pathogenic potentials in vivo. Individuals who are infected with one BKV serotype may remain humorally vulnerable to other BKV serotypes after implementation of T cell immunosuppression. Thus, prevaccinating organ transplant recipients with a multivalent BKV VLP vaccine might reduce the risk of developing posttransplant BKV disease.
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Spatial mapping of gene expression in the salivary glands of the dengue vector mosquito, aedes aegypti
Juhn, Jennifer
Naeem-Ullah, Unsar
Maciel Guedes, Bruno Augusto
Majid, Asif
Coleman, Judy
Paolucci Pimenta, Paulo Filemon
Akram, Waseem
James, Anthony Amade
Marinotti, Osvaldo
Parasites & Vectors
Aedes aegypti mosquitoes are the main vectors of dengue viruses to humans. Understanding their biology and interactions with the pathogen are prerequisites for development of dengue transmission control strategies. Mosquito salivary glands are organs involved directly in pathogen transmission to vertebrate hosts. Information on the spatial distribution of gene expression in these organs is expected to assist in the development of novel disease control strategies, including those that entail the release of transgenic mosquitoes with impaired vector competence.
We report here the hybridization in situ patterns of 30 transcripts expressed in the salivary glands of adult Ae. aegypti females. Distinct spatial accumulation patterns were identified. The products of twelve genes are localized exclusively in the proximal-lateral lobes. Among these, three accumulate preferentially in the most anterior portion of the proximal-lateral lobe. This pattern revealed a salivary gland cell type previously undescribed in Ae. aegypti, which was validated by transmission electron microscopy. Five distinct gene products accumulate in the distal-lateral lobes and another five localize in the medial lobe. Seven transcripts are found in the distal-lateral and medial lobes. The transcriptional product of one gene accumulates in proximal- and distal-lateral lobes. Seven genes analyzed by quantitative PCR are expressed constitutively. The most abundant salivary gland transcripts are those localized within the proximal-lateral lobes, while previous work has shown that the distal-lateral lobes are the most active in protein synthesis. This incongruity suggests a role for translational regulation in mosquito saliva production.
Transgenic mosquitoes with reduced vector competence have been proposed as tools for the control of dengue virus transmission. Expression of anti-dengue effector molecules in the distal-lateral lobes of Ae. aegypti salivary glands has been shown to reduce prevalence and mean intensities of viral infection. We anticipate greater efficiency of viral suppression if effector genes are expressed in all lobes of the salivary glands. Based on our data, a minimum of two promoters is necessary to drive the expression of one or more anti-dengue genes in all cells of the female salivary glands.
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A Focused Salivary Gland Infection with attenuated MCMV: An Animal Model with Prevention of Pathology Associated with Systemic MCMV Infection1, 2
Pilgrim, Mark J.
Kasman, Laura
Grewal, Jasvir
Bruorton, Mary E.
Werner, Phil
London, Lucille
London, Steven D.
Experimental and molecular pathology
While the salivary gland has been recognized as an important effector site of the common mucosal immune system, a useful model for studying anti-viral salivary gland immune responses in vivo and for exploring the role of the salivary gland within the common mucosal system has been lacking. Murine cytomegalovirus (MCMV) is a beta-herpesvirus that displays a strong tropism for the salivary gland and produces significant morbidity in susceptible mice when introduced by intraperitoneal (i.p.) inoculation. This study tested the hypothesis that MCMV morbidity and pathology could be reduced by injecting the virus directly the submandibular salivary gland (intraglandular (i.g.)), using either in vivo derived MCMV or the less virulent, tissue culture-derived MCMV (tcMCMV). Peak salivary gland viral titers were completely unaffected by infection route (i.p vs. i.g.) after inoculation with either MCMV or tcMCMV. However, i.g. tcMCMV inoculation reduced viremia in all systemic tissues tested compared to i.p. inoculation. Further, systemic organ pathology observed in the liver and spleen after i.p. inoculation with either MCMV or tcMCMV was completely eliminated by i.g. inoculation with tcMCMV. Cellular infiltrates in the salivary glands, after i.p. or i.g. inoculation were composed of both B and T cells, indicating the potential for a local immune response to occur in the salivary gland. These results demonstrate that a focused MCMV infection of the salivary gland without systemic organ pathology is possible using i.g. delivery of tcMCMV.
rodent; viral; MCMV; mucosa; spleen and lymph nodes; salivary gland; antibodies; mucosal immunity
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Frequent Detection of Polyomaviruses in Stool Samples from Hospitalized Children
Vanchiere, John A.
Nicome, Roger K.
Greer, Jewel M.
Demmler, Gail J.
Butel, Janet S.
The Journal of infectious diseases
Infection with BK virus (BKV) generally occurs early during life, but its mode of transmission has not been clearly defined. We tested the hypothesis that polyomavirus shedding in stool may be a source of BKV exposure.
Pediatric stool and rectal swab samples were tested for the presence of polyomavirus DNA by a polymerase chain reaction (PCR) assay that could detect a conserved region in the large T antigen gene of BKV, JC virus (JCV), and simian virus 40 (SV40). The specific viruses detected by this assay were confirmed by DNA sequence analysis of the PCR amplicons.
Of 120 samples collected from 99 patients, 54 (45.0%) were positive for polyomavirus DNA. Of the 99 patients, 46 (46.5%) had at least 1 positive sample, with 38 (38.4%) positive for BKV and 8 (8.1%) positive for SV40. JCV was not detected. There was no association between polyomavirus fecal shedding and age, sex, race/ ethnicity, immune status, or symptoms of gastrointestinal disease in the children studied. The BKV strains detected displayed polymorphisms in the T antigen sequence.
Polyomaviruses are frequently present in stool samples from hospitalized children. These findings suggest that fecal-oral transmission of BKV may play a role in the ubiquity of infection.
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Salivary Gland Hypofunction Induced by Activation of Innate Immunity is Dependent on Type I Interferon Signaling
Nandula, Seshagiri-Rao
Dey, Paromita
Corbin, Kathryn L.
Nunemaker, Craig
Bagavant, Harini
Deshmukh, Umesh S.
Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology
Activation of innate immunity through polyinosinic:polycytidylic acid (poly(I:C)) causes acute salivary gland hypofunction. Since a major consequence of poly(I:C) treatment is type I interferon (IFN) production, this study was undertaken to investigate their role in salivary gland dysfunction.
Different strains of mice, deficient either in interferon alpha receptor (IFNAR1−/−), or IL-6−/−, or IL-10−/−, or EBI3−/− were treated with poly(I:C). Salivary gland function was determined by measuring pilocarpine induced saliva volume. Gene expression levels were measured by real time PCR. Ca2+ mobilization studies were done using ex-vivo acinar cells.
A single injection of poly(I:C) rapidly induced salivary gland hypofunction in wild type B6 mice (41% drop in saliva volumes compared to PBS treated mice). In contrast, the loss of function in poly(I:C) treated IFNAR−/− mice was only 9.6%. Gene expression analysis showed reduced levels of Il-6, Il-10 and Il-27 in submandibular glands of poly(I:C) treated IFNAR−/− mice. While salivary gland dysfunction in poly(I:C) treated IL-10−/− and EBI3−/− mice was comparable to wild type mice, the IL-6−/− mice were more resistant, with only a 21 % drop in function. Pilocarpine induced Ca2+ flux was significantly suppressed in acinar cells obtained from poly(I:C) treated wild type mice.
Our data demonstrates that a combined action of type I IFNs and IL-6 contributes towards salivary gland hypofunction. This happens through interference with Ca2+ mobilization within acinar cells. Thus, in acute viral infections and diseases like Sjögren's syndrome, elevated levels of type I IFNs and IL-6 can directly affect glandular function.
Xerostomia; Sjogren's syndrome; Innate Immunity; Interferon
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Natural Killer Cells Regulate Murine Cytomegalovirus-Induced Sialadenitis and Salivary Gland Disease
Carroll, Virginia A.
Lundgren, Alyssa
Wei, Hairong
Sainz, Susan
Tung, Kenneth S.
Brown, Michael G.
Journal of Virology
The transmission of herpesviruses depends on viral shedding at mucosal surfaces. The salivary gland represents a major site of persistent viral replication for many viruses, including cytomegalovirus. We established a mouse model of salivary gland dysfunction after acute viral infection and investigated the cellular requirements for the loss of secretion. Murine cytomegalovirus (MCMV) infection severely impaired saliva secretion independently of salivary gland virus levels. Lymphocytes or circulating monocytes/macrophages were not required for secretory dysfunction. Dysfunction occurred before glandular inflammation, suggesting that a soluble mediator initiated the disruption of acinar cell function. Despite genetic differences in innate resistance to MCMV, NK cells protected the host against acinar atrophy and the loss of secretions under conditions of an exceedingly low virus inoculum. NK cells also modulated the type of glandular inflammation after infection, as they prevented an influx of Siglec-F+ polymorphonuclear leukocytes (PMNs). Therefore, beyond their recognized role in controlling MCMV replication, NK cells preserve organ integrity and function and regulate the innate inflammatory response within the gland.
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Polyomavirus Infection and Its Impact on Renal Function and Long-Term Outcomes after Lung Transplantation
Thomas, Lora D.
Milstone, Aaron P.
Vilchez, Regis A.
Zanwar, Preeti
Butel, Janet S.
Dummer, J. Stephen
Polyomavirus infection causes nephropathy after kidney transplantation but has not been thoroughly investigated in nonrenal organ transplantation.
Ninety lung transplant recipients were enrolled and provided urine samples over 4.5 years. Samples were analyzed for BK virus (BKV), JC virus (JCV), and simian virus 40 (SV40) by conventional and quantitative real time polymerase chain reaction (PCR).
Fifty-nine (66%) patients had polyomavirus detected at least once, including 38 (42%) for BKV, 25 (28%) for JCV, and 6 (7%) for SV40. Frequency of virus shedding in serial urine samples by patients positive at least once varied significantly among viruses: JCV, 64%; BKV, 48%; SV40, 14%. Urinary viral loads for BKV (105.4copies/ml) and JCV (106.0 copies/ml) were higher than for SV40 (102.5 copies/ml; p=0.001 and p=0.0003, respectively). Polyomavirus infection was associated with a pre-transplant diagnosis of chronic obstructive pulmonary disease [odds ratio (OR) = 6.0; p=0.016], but was less common in patients with a history of acute rejection [OR=0.28; p=0.016]. SV40 infection was associated with sirolimus-based immunosuppression (p=0.037). Reduced survival was noted for patients with BKV infection (p=0.03). Patients with polyomavirus infection did not have worse renal function than those without infection, but in patients with BKV infection, creatinine clearances were lower at times when viral shedding was detected (p=0.038).
BKV and JCV were commonly detected in the urine of lung transplant recipients; SV40 was found at low frequency. No definite impact of polyomavirus infection on renal function was documented. BKV infection was associated with poorer survival.
Polyomavirus; lung transplantation; kidney disease
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Functional salivary gland regeneration by transplantation of a bioengineered organ germ
Ogawa, Miho
Oshima, Masamitsu
Imamura, Aya
Sekine, Yurie
Ishida, Kentaro
Yamashita, Kentaro
Nakajima, Kei
Hirayama, Masatoshi
Tachikawa, Tetsuhiko
Tsuji, Takashi
Nature Communications
Salivary gland hypofunction, also known as xerostomia, occurs as a result of radiation therapy for head cancer, Sjögren's syndrome or aging, and can cause a variety of critical oral health issues, including dental decay, bacterial infection, mastication dysfunction, swallowing dysfunction and reduced quality of life. Here we demonstrate the full functional regeneration of a salivary gland that reproduces the morphogenesis induced by reciprocal epithelial and mesenchymal interactions through the orthotopic transplantation of a bioengineered salivary gland germ as a regenerative organ replacement therapy. The bioengineered germ develops into a mature gland through acinar formations with a myoepithelium and innervation. The bioengineered submandibular gland produces saliva in response to the administration of pilocarpine and gustatory stimulation by citrate, protects against oral bacterial infection and restores normal swallowing in a salivary gland-defective mouse model. This study thus provides a proof-of-concept for bioengineered salivary gland regeneration as a potential treatment of xerostomia.
Salivary gland dysfunction as a result of diseases or ageing reduces the quality of life and causes various oral health problems. Here the authors show that the salivary gland function of mice can be recovered by orthotopic transplantation of a bioengineered salivary gland germ.
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I think I do a decent job of backing up my data on my various devices. I have everything ranging from old emails to various photos I've taken throughout the years. I don't want to lose my stuff under any circumstances, whether because a system died or I lost an external hard drive. But despite…Read More
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There are few reliable statistics indicating the exact size of the global ransomware epidemic. But according to the FBI, just one variant – CryptoWall – netted its authors over $18 million in just over a year. It's pretty clear that this is the black hats' new favorite way to extort money from their victims. That's…Read More
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The International Federation of Catholic Doctors Associations has come to the defense of a Spanish bishop prelate who has encountered heavy criticism for his comments on the self-destructive practices of active homosexuals. Read more here.
Brother Andre MarieEpisode 25. Corpus Christi, Feast and Mystery. Guest: Sister Maria Philomena, M.I.C.M. https://t.co/WdDs6KZnJv https://t.co/23luF9sDKt4 hours ago 1
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This entry was posted in Morals, News and tagged Bishop Juan Antonio Reig Pla, homosexual activism, International Federation of Catholic Doctors Associations. Bookmark the permalink.


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