in december 1999 , a 75-year - old man from vancouver , british columbia , canada , arrived at the hospital with severe zoster lesions on his face ( in division v1 of the left trigeminal cranial nerve ) . painful postherpetic neuralgia with headaches , associated with occasional blurring of vision and lasting for 6 months , developed . the patient was treated with famciclovir ( 500 mg three times a day for 7 days ) . a swab of the facial vesicles was obtained from the patient during acute zoster before famciclovir treatment . results of immunofluorescence staining , performed with a commercial kit ( meridian diagnostics , cincinnati , oh ) by using the anti - ge monoclonal antibody ( mab 3b3 ) , were negative . staining with monoclonal antibody conjugates for cytomegalovirus and human herpes simplex viruses was also negative . polymerase chain reaction amplification and subsequent dna sequencing confirmed the virus genome to be vzv ( hereafter referred to as vzv - bc ) . the vzv - bc strain was then analyzed in orf68 ( encodes ge and contains the 3b3 mab epitope ) and found to have an identical nucleotide sequence to vzv - msp ( genbank accession no . the vzv - bc and vzv - msp strains differed from the prototype dumas vzv strain ( genbank accession no . x04370 ) in orf68 by a single g448a nucleotide mutation ( d150n amino acid substitution ) in the 3b3 epitope of ge ( table ) . vzv - msp and vzv - bc were also identical in nucleotide sequence in orf62 ( ie62 ) and orf37 ( gh ) . in short , vzv - bc was closely related genetically , if not identical , to the vzv - msp mutant virus . vzv - bc , varicella - zoster virus found in british columbia ; vzv - msp , varicella - zoster virus glycoprotein e mutant virus . vzv - msp was the first community - acquired vzv strain shown to have a phenotype distinguishable from the traditional vzv phenotype . this case report documents the existence of a second isolate with the same ge genotype . vzv - msp has been shown to have attributes consistent with increased virulence in the scid - hu mouse model ( 2 ) . both vzv - msp and vzv - bc are escape mutants ( i.e. , they have lost a b - cell epitope present in the prototypic dumas virus from holland , as well as other viruses from north america , europe , and asia , including the oka varicella vaccine strain from japan ) ( 11 ) . we have previously shown that the same ge epitope is involved in both complement - dependent neutralization ( 12 ) as well as antibody - dependent cellular cytotoxicity ( 13 ) . considering the cell culture and animal model data for vzv - msp and the lost b - cell epitope resulting from the d150n ge mutation , this mutation should be monitored to determine whether it plays a role in more severe cases of varicella or zoster or in breakthrough varicella in previously immunized children . the origin of this variant may be the same ge mutation , occurring separately in two patients by chance . the argument favoring chance was raised after the discovery of the first ge mutant ; however , we find this argument less compelling after the discovery of a second vzv strain with an identically mutated ge antigenic site , just 4 years later . the same ge mutation may have occurred from selective antibody pressure . in an article from the laboratory of the nobel laureate zinkernagel ( 14 ) , the investigators showed that antibody escape variant viruses were more likely to arise in animals with deficient cellular immunity . the original vzv - msp isolate was obtained from chickenpox in a child under treatment for leukemia , a condition known to be associated with depressed immunity . the second isolate was obtained from an elderly adult with herpes zoster , a condition that may be related to diminished immunity from aging . one of the antibody - escape glycoprotein mutant viruses described by the zinkernagel laboratory had the identical aspartic acid to asparagine mutation seen in the two vzv - msp glycoprotein variant viruses . the most likely scenario is that vzv - msp is a previously unrecognized subpopulation of vzv that has been circulating for more than 50 years in circumscribed regions of northern united states and canada . the timeline is based on the decade when the british columbia patient likely first contracted chickenpox as a child . ( 15 ) did not uncover a d150n ge mutation ; therefore , larger studies need to be conducted to determine the prevalence of this mutant virus in north america . we conclude that diagnosticians should be aware of the existence of vzv - msp - like strains and the potential for false - negative testing results with single mab - based antigen - detection kits for vzv or other herpesviruses . further clinical observations are needed to fully assess the biological significance of the vzv ge mutant virus .
in 1998 , a varicella - zoster virus glycoprotein e ( ge ) mutant virus ( vzv - msp ) was isolated from a child with chickenpox . 
 vzv - msp , representing a second vzv serotype , was considered a rarity . 
 we isolated another vzv - msp - like virus from an elderly man with herpes zoster . 
 these ge mutant viruses may have arisen through independent mutation or may represent a distinct vzv subpopulation that emerged more than 50 years ago .