 conditions, which are influenced by both genetic and epigenetic factors, result from the inappropriate activity of a polypeptide as opposed to the complete loss of its function. Accordingly, antagonizing the aberrant function of such mutant genes would provide a means of treatment. Additionally, infectious diseases such as HIV have been successfully treated with molecular antagonists targeted to specific essential retroviral proteins such as HIV protease or reverse transcriptase. Drug therapy strategies for treating such diseases and disorders have frequently employed molecular antagonists which target the polypeptide product of the disease gene(s). However the discovery of relevant gene or protein targets is often difficult and time consuming.
One area of particular interest is the identification of host genes and proteins that are co-opted by viruses during the viral life cycle. The serious and incurable nature of many viral diseases, coupled with the high rate of mutations found in many viruses, makes the identification of antiviral agents a high priority for the improvement of world health. Genes and proteins involved in a viral life cycle are also appealing as a subject for investigation because such genes and proteins will typically have additional activities in the host cell and may play a role in other non-viral disease states.
Viral maturation involves the proteolytic processing of the Gag proteins and the activity of various host proteins. It is believed that cellular machineries for exo/endocytosis and for ubiquitin conjugation may be involved in the maturation. In particular, the assembly, budding and subsequent release of retroid viruses, RNA viruses and envelop viruses, such as various retroviruses, rhabdoviruses, lentiviruses, and filoviruses may involve the Gag polyprotein. After its synthesis, Gag is targeted to the plasma membrane where it induces budding of nascent virus particles.
The role of ubiquitin in virus assembly was suggested by Dunigan et al. (1988, Virology 165, 310, Meyers et al. 1991, Virology 180, 602), who observed that mature virus particles were enriched in unconjugated ubiquitin. More recently, it was shown that proteasome inhibitors suppress the release of HIV-1, HIV-2 and virus-like particles derived from SIV and RSV Gag. Also, inhibitors affect Gag processing and maturation into infectious particles (Schubert et al 2000, PNAS 97, 13057, Harty et al. 2000, PNAS 97, 13871, Strack et al. 2000, PNAS 97, 13063, Patnaik et al. 2000, PNAS 97, 13069).
It is well
conditions, which are influenced by both genetic and epigenetic factors, leave from the inappropriate natural process of a polypeptide as opposed to the complete personnel casualty of its routine. Accordingly, antagonizing the aberrant routine of such mutant gene would provide a means of treatment. Additionally, infectious diseases such as HIV have been successfully treated with molecular antagonist targeted to specific essential retroviral protein such as HIV protease or reverse transcriptase. Drug therapy strategies for treat such diseases and disorders have frequently use molecular antagonists which target the polypeptide product of the disease gene(s). However the discovery of relevant gene or protein targets is much difficult and time consuming. 
 One area of especial interest is the identification of host genes and proteins that are co - choose by viruses during the viral life cycle. The serious and incurable nature of many viral diseases, coupled with the eminent rate of mutations found in many viruses, makes the identification of antiviral agents a high priority for the improvement of world health. gene and protein involved in a viral life cycle are besides attract as a subject for investigation because such genes and proteins will typically have additional activities in the server cell and may play a role in other non - viral disease states. 
 Viral maturation involve the proteolytic processing of the Gag proteins and the activity of various host protein. It is believed that cellular machinery for exo / endocytosis and for ubiquitin union may be involved in the maturation. In particular, the assembly, budding and subsequent acquittance of retroid viruses, RNA viruses and envelop viruses, such as various retroviruses, rhabdoviruses, lentiviruses, and filoviruses may involve the Gag polyprotein. After its deduction, Gag is targeted to the plasma membrane where it induces budding of nascent virus particles. 
 The role of ubiquitin in virus fabrication was suggested by Dunigan et al. (1988, Virology 165, 310, Meyers et al. 1991, Virology 180, 602), who observe that mature virus atom were enriched in unconjugated ubiquitin. More recently, it was show that proteasome inhibitors suppress the release of HIV-1, HIV-2 and virus - like particles deduce from SIV and RSV Gag. Also, inhibitor affect Gag processing and maturation into infectious particles (Schubert et al 2000, PNAS 97, 13057, Harty et al. 2000, PNAS 97, 13871, Strack et al. 2000, PNAS 97, 13063, Patnaik et al. 2000, PNAS 97, 13069). 
 It is well
 cojditions, which are influtnced by both gengtuc and epigehetic faztors, result from the inapprlpeiate activity of a polypepgide as oiposed to the xomplete loss of ibf fuhgtion. Eccordingly, antsgonizing dhe aberrant fgnztnon of such mutant genes would proviqe a mesnd of treatment. Addptyonamly, infectious diseases such as HIB have ueen successfulky treated with molecular wntahonists targeted tl specific gasegrial retrovifal proteins such as HJV protease or reverse transcriotase. Drug therqpt shtategies for treaning such discsses atd disotders have freaueitly employed molecular aitagonists which tardet the pmlvpeptide product of tye disedse cene(r). Hodevtr vhe discogerb of relevaht gene or protein targets is pfevm difficult znd tiie consuming.
One area of particular interevt js the identification od host genes and protgins that wre co-opted by viruses during the viral life cycla. The rernius ave lncurable nature of many viral diseases, couplqs einh the high rate jf mutationx voigd in many vituses, mciea the identificatiln of agtivieal agentf a nigh priority for the improcement of wogld yealth. Genes and pxoteins invouved in a viral life cycle are auso zppealing ad a subjedg for investigatkon bacause such genes and protqins will typncally hxve sdditijnal activlties in the host cell ajd mai play a role in other non-viral disease states.
Vmcal maturatiom hnvmlves thz protcolytic processyng of the Gag proteius and the activpty of vacious host pwoteins. It is helieved thav cellulaw maxhinwries fuf exo/endocytosos and fog bbiquitin conjugation may bc invumved in the matbxauiin. In particulsr, ghe adsxmbly, tudding and vubsdqudmt reuease of rebrokd voruses, RNA viruses atd ehvelop viruses, sucn ws varioos retrovyruses, rhabdofiruses, lentivirusts, and fiuovirisef may involve the Gag polyprotsin. After itf synthesis, Dag ls twrgeted to the plasma membrane where it induces bndding of nascent virus particles.
The role pn ubiquitin mn virts assembny was suggested by Eunigan et al. (1988, Vivology 165, 310, Meyers et al. 1991, Virolmgy 180, 602), who observed that mature virus particles were enriched in unconjugated uviquitmn. More recenfly, ot wav fkown thwt pcoveasome inhibitorx suppress the release of HIV-1, HMV-2 and virgs-jike particles derived from XIX and RSV Gag. Also, inhibitors affect Fag procrssing and maturation into infevtious particles (Schuberb et al 2000, PNAS 97, 13057, Hartj ev al. 2000, PNAS 97, 13871, Strack rt al. 2000, PNAS 97, 13063, Patnqik ct al. 2000, PNAS 97, 13069).
Ig ix aell
conditions, which are influenced by both genetic factors, from the activity of a complete of its function. antagonizing the aberrant of such mutant genes would provide means of treatment. Additionally, infectious diseases such as HIV have been successfully treated molecular antagonists targeted to specific essential retroviral proteins such as HIV protease or transcriptase. therapy for such diseases and disorders have frequently employed molecular antagonists which target the polypeptide product of the gene(s). However the discovery of relevant gene or targets is often difficult time consuming. One area of interest the identification host and that are co-opted viruses during the viral life cycle. The serious and incurable nature of many viral diseases, coupled with high rate found in viruses, the of antiviral agents priority for the improvement of world proteins involved in a viral life cycle are appealing as subject for investigation because such genes proteins will typically have additional activities in the cell and may play a role in other non-viral disease states. Viral maturation involves the of the Gag proteins the activity of host It believed cellular machineries exo/endocytosis and for ubiquitin conjugation may be involved in the maturation. particular, the assembly, budding and subsequent release of retroid viruses, and viruses, such as retroviruses, rhabdoviruses, lentiviruses, and may the Gag polyprotein. After Gag targeted membrane it budding of nascent virus The role of ubiquitin in assembly was suggested by 165, 310, Meyers et al. 1991, Virology 180, who observed that mature virus particles were in unconjugated ubiquitin. More recently, it was shown that proteasome inhibitors suppress release of and virus-like particles derived from SIV and RSV Also, inhibitors affect Gag and maturation into infectious particles (Schubert et al 2000, 97, Harty et 2000, PNAS 97, Strack et al. PNAS 97, 13063, al. 2000, 97, It
 conditions, which are influenCed by both gEnetiC anD epIgEnetIc faCtors, result froM The iNappropriate activity of A polyPePTide AS oPposeD to the cOMpLETe lOsS oF itS fUNcTion. ACcoRdingly, AntagoniziNg tHe Aberrant funcTIoN of such mutAnt Genes would prOviDe a meaNs Of tREatmeNt. ADditiOnally, INfectiOus diseasEs SUch as Hiv have beEN SuCcesSfully treated with MOlECular antagonisTs targEtED tO SPecIfiC essential ReTroviRAl proteINs SUCH as hiV protease or rEverse transCRipTase. DrUg TheRApy strAtegiEs FOr tReating such DiseAses and diSorderS Have freQUently eMployeD moLecUlar ANtAgOniStS WhiCH tArgET thE polypepTiDe ProduCt of THE DIseaSe gEne(s). howevEr the discoverY of ReleVAnt Gene oR protEin tArGets iS often DiffiCuLt and time consumIng.
ONe area of pArtIcUlaR iNtereST is the IdeNtiFicatioN of host GEneS aND PRoTeins that are co-opteD bY VIrUses duriNg the vIRaL lIFe cycle. THe SerIous AND incuRablE NaTure of maNy viraL DiSeAses, couPlEd with ThE hiGh rAte of MUtatIons foUnd in manY viruSEs, makes the idenTIfication of anTIvIRAl AGentS a hIgh priority For tHE impRoveMEnT of WOrld hEalth. geNEs ANd proteins involved iN a Viral lIfe cyCle are also appEaling as a sUBJEct for inVestIGaTIon because such Genes And proteinS Will typiCally Have addiTional actIVIties in tHe hOst CelL anD MAy Play a role in otHER non-ViRal diseAse States.
VIraL maTurAtiOn Involves tHe proteoLyTiC pRoCesSing oF The Gag prOtEinS aNd tHe actIVity of VarioUs hoSt PrOTeiNs. It is bELiEVEd thAt CeLlulAr mAcHinerIes fOR exO/endocyTosis and fOr uBIquiTiN cOnjugatIon may be involVeD in the matuRaTioN. In parTICular, the Assembly, budding and subseQUent relEasE of reTroiD viruses, RnA vIruses And ENvelop ViruseS, such As VarIOUs retROViRusEs, RhabdoviruSES, leNtiviRuSes, aNd filovIruses may involve thE gag Polyprotein. AfTer Its sYNThEsiS, gaG Is tArGEteD TO the plasma membrAne where it InDUcEs budding oF NasCeNt virus ParticlEs.
The ROle of ubIquitin in Virus asseMbLy waS SUggEsted by DunIgan et al. (1988, virology 165, 310, MEYers eT Al. 1991, virolOgy 180, 602), Who obsErVed That mAture vIRus PartiCles weRe EnrichEd in uNcOnjugateD ubiquitin. More recently, iT was shOwn thAt pRoteasome InhIBitOrs suppreSs thE release of hIV-1, hIV-2 And viRus-LIke paRticLEs DerIVed frOm SIv And RSV Gag. aLsO, inHIBiTors affect GAG PRocEssinG anD MaturaTion Into infectious parTIcles (Schubert eT al 2000, Pnas 97, 13057, HaRty ET al. 2000, PnAs 97, 13871, Strack et al. 2000, PNAs 97, 13063, PaTnAIK et al. 2000, PNAs 97, 13069).
IT is well
 conditions, which are inf luenced by  both  ge net ic  and  epi genetic factor s , re sult from the inapprop riate  a c tivi t yof apolypep t id e asop po sed  t o  t he co mpl ete los s of its f unc ti on. Accordin g ly , antagoni zin g the aberra ntfuncti on  of suchmut ant g enes w o uld pr ovide a m ea n s of t r eatment . Ad diti onally, infectiou s  d i seases such as  HIV h av e  b e e n s ucc essfully t re atedw ith mol e cu l a r  an t agonists targ eted to spe c ifi c esse nt ial retrov iralpr o tei ns such asHIVproteaseor rev e rse tra n scripta se. Dr ugthe rapy st ra teg ie s  fo r  t rea t ing  such di se as es an d di s o r d ershav e fr equen tly employedmol ecul a r a ntago nists  whi ch  targ et the  poly pe ptide product o f th e disease  ge ne (s) .Howev e r thedis cov ery ofrelevan t  ge ne o r  p rotein targets isof t e ndifficul t andt im ec onsuming .One  are a of pa rtic u la r intere st ist he  i dentifi ca tion o fhos t g enesa nd p rotein s that a re co - opted by virus e s during thev ir a l  l i fe c ycl e. The seri ousa nd i ncur a bl e n a tureof ma ny vi r al diseases, couple dwith t he hi gh rate of mu tations fo u n d  in many  vir u se s , makes the id entif ication of antivira l age nts a hi gh priori t y  for the  im pro vem ent o fworld health. G enes  a nd prot ein s invol ved  in  avir al  life cyc le are a ls oap pe ali ng as a subjec tfor  i nve stiga t ion be cause  suc hge n esand pro t ei n s  wil lty pica lly  h ave a ddit i ona l activ ities inthe host  c el l and m ay play a rol ein other n on -vi ral di s e ase stat es.
Viral maturation in v olves t heprote olyt ic proces sin g of t heG ag pro teinsand t he  ac t i vityo f  v ari ou s host pro t e ins . Itis  bel ieved t hat cellular machi n eri es for exo/en doc ytos i s  a ndf or ubi qu i tin c onjugation maybe involve di nthe matura t ion .In part icular,  thea ssembly , budding  and subs eq uent r ele ase of ret roid vir uses, RNA virus e sand e nve lop vi ru ses , suc h as v a rio us re trovir us es, rh abdov ir uses, le ntiviruses, and filovir uses m ay in vol ve the Ga g p o lyp rotein. A fter  its synth esi s,Gag i s t a rgete d to th e p l asmamemb r ane where it  in d u ce s budding o f n asc ent v iru s  parti cles .
The role of ubi q uitin in virus  ass e m bly  wa s  sug ge sted by Duniga n e ta l . (1988,  V irology 165 , 310, M ey e rs et  al. 1 991, V irology 1 80 ,  602),  who  ob served th atma t ure vir us  p a rticle s we re  enric hed in unco n j ugated ubiquitin . Mor e recen t ly,  it w as  shownt hatproteasome  inhibitors  suppr essthe r eleaseof  HIV-1 , H IV -2 and vir u s-like pa rticl es deri ve d fr omSIV an d RS V Gag.Also ,inh ibitors a f f ec t  G ag pro cess ing a nd  mat uration i n to infec tio u s parti cl es( S chuber t  e t al 2000, P NAS  97,1 3 057, Harty et a l .2 000,PNAS 9 7, 138 71, Str a cket  al. 20 00, P NAS 97, 1 3063, Pat n aik  e t al . 2000,PN AS 9 7,  13 06 9).
It is well
 conditions,_which are_influenced by both genetic_and epigenetic_factors,_result from_the_inappropriate activity of_a polypeptide as_opposed to the complete_loss of its_function._Accordingly, antagonizing the aberrant function of such mutant genes would provide a means of_treatment._Additionally, infectious_diseases_such_as HIV have been successfully_treated with molecular antagonists targeted_to specific_essential retroviral proteins such as HIV protease or_reverse_transcriptase. Drug therapy_strategies for treating such diseases and disorders have frequently_employed molecular antagonists which target the_polypeptide product of_the_disease_gene(s). However the discovery_of relevant gene or protein targets_is often difficult and time consuming.
One_area of particular interest is the identification_of host genes and proteins that_are co-opted by viruses during_the viral_life cycle. The serious and_incurable nature of_many viral_diseases, coupled with_the high rate of mutations found_in many viruses,_makes the identification of antiviral agents_a_high priority for_the_improvement_of world_health. Genes and_proteins_involved in_a_viral life cycle are also appealing_as_a subject for investigation because such genes_and proteins will typically_have_additional activities in the_host cell and may play_a role in other non-viral disease_states.
Viral maturation_involves the_proteolytic processing of the Gag proteins and the activity of various_host proteins. It is believed that_cellular machineries for exo/endocytosis_and for_ubiquitin_conjugation may be_involved_in the_maturation. In particular, the assembly, budding and_subsequent release_of retroid viruses, RNA viruses and_envelop viruses, such as_various_retroviruses, rhabdoviruses, lentiviruses, and filoviruses may_involve the Gag polyprotein. After its_synthesis, Gag is targeted to_the_plasma_membrane where it induces budding_of nascent virus particles.
The role of_ubiquitin in virus_assembly was suggested by Dunigan et al._(1988,_Virology 165, 310, Meyers et al._1991,_Virology 180, 602), who observed that_mature_virus_particles were enriched in unconjugated_ubiquitin. More recently, it was shown_that proteasome inhibitors suppress the release of HIV-1, HIV-2_and virus-like particles_derived from SIV and RSV_Gag._Also,_inhibitors affect Gag processing and maturation into infectious particles (Schubert_et al_2000, PNAS 97,_13057, Harty et al. 2000, PNAS 97, 13871, Strack et_al. 2000, PNAS 97, 13063, Patnaik et_al. 2000, PNAS 97, 13069).
It is well