Mark Quinlivan

Of 75 varicella-zoster virus (VZV) isolates obtained from patients in Africa, Asia, and the Far East, 74 (98.6%) were found to be positive for a BglI restriction site in gene 54. By contrast, <22% of strains from patients in the United Kingdom and in North and South America were positive for the BglI restriction site. Viruses positive for BglI were significantly more common in zoster occurring in patients of nonwhite origin (P<.05). Irrespective of the country in which the sample was obtained, 98% of strains positive for BglI clustered within a single phylogenetic group, which we termed "group A"; the exception was 1 strain that appeared to be recombinant genotype C/A. We used the BglI site to examine both the spread of type A viruses in the United Kingdom and the patterns of VZV infections within persons from different ethnic groups who grew up in the United Kingdom or abroad.

VZV is a highly cell-associated member of the Herpesviridae family and one of the eight herpesviruses to infect humans. The virus is ubiquitous in most populations worldwide, primary infection with which causes varicella, more commonly known as chickenpox. Characteristic of members of the alphaherpesvirus sub-family, VZV is neurotropic and establishes latency in sensory neurones. Reactivation from latency, usually during periods of impaired cellular immunity, causes herpes zoster (shingles). Despite being one of the most genetically stable human herpesviruses, nucleotide alterations in the virus genome have been used to classify VZV strains from different geographical regions into distinct clades. Such studies have also provided evidence that, despite pre-existing immunity to VZV, subclinical reinfection and reactivation of reinfecting strains to cause zoster is also occurring. During both primary infection and reactivation, VZV infects several PBMC and skin cell lineages. Difficulties in studying the pathogenesis of VZV because of its high cell association and narrow host range have been overcome through the development of the VZV severe combined immunodeficient mouse model carrying human tissue implants. This model has provided a valuable tool for studying the importance of individual viral proteins during both the complex intracellular replication and assembly of new virions and for understanding the underlying mechanism of attenuation of the live varicella vaccine. In addition, a rat model has been developed and successfully used to uncover which viral proteins are important for both the establishment and maintenance of latent VZV infection.

Varicella-zoster virus vaccine has diminished the consequences of chicken pox in terms of health and economical burden. The increasing number of doses administered worldwide has revealed rare but important adverse effects that had not occurred during clinical trials. We report here the case of an immunocompetent 3(1/2)-year-old girl who developed encephalitis and herpes zoster opthalmicus 20 months after her immunization with varicella-zoster virus vaccine. Molecular analysis confirmed the vaccine strain as the causative agent. After an intravenous course with acyclovir, the child made a full recovery with no neurologic sequelae.

Single nucleotide polymorphisms (SNPs) in five genes have been used to identify four major subtypes of wild-type varicella-zoster virus (VZV) A, B, C, and J. Additional SNPs, located in the IE62 major transactivating gene can be used to differentiate the Oka vaccine strain (vOka) from wild-type VZV. Primer-probe sets for the detection of the five polymorphic loci were designed by Applied Biosystems for the ABI 7900HT platform. Probes for each allele were labeled with VIC or 6-carboxyfluorescein fluorogenic markers. Each primer-probe set was validated to establish assay sensitivity and specificity using VZV DNA of predetermined copy number and genotype. Further evaluation was carried out using DNA samples from the vesicle fluid or skin swab of the rash of adult patients with herpes zoster or rashes due to vOka. Assay sensitivity ranged from 10 and 10(8) copies/ml of VZV DNA (equivalent to 2 to 20 copies per reaction). Statistical analyses showed that for each genotype, a set of two probes clearly differentiated the nucleotide present (allele) at that locus (P < 0.0001). It was possible to determine the genotype of wild-type VZV using one of four SNP assays and also to differentiate wild type from vOka using a single SNP assay. The assay can be used for diagnostic and epidemiological studies of VZV, including the differentiation of vOka from wild-type strains, investigation of breakthrough infections, and varicella outbreaks following immunization.