Varicella-Zoster Virus Neurotropism in SCID Mouse–Human Dorsal Root Ganglia Xenografts

ABSTRACT Varicella-zoster virus (VZV) expresses at least six viral transcripts during latency. One of these transcripts, derived from open reading frame 63 (ORF63), is one of the most abundant viral RNAs expressed during latency. The VZV ORF63 protein has been detected in human and experimentally infected rodent ganglia by several laboratories. We have deleted >90% of both copies of the ORF63 gene from the VZV genome. Animals inoculated with the ORF63 mutant virus had lower mean copy numbers of latent VZV genomes in the dorsal root ganglia 5 to 6 weeks after infection than animals inoculated with parental or rescued virus, and the frequency of latently infected animals was significantly lower in animals infected with the ORF63 mutant virus than in animals inoculated with parental or rescued virus. In contrast, the frequency of animals latently infected with viral mutants in other genes that are equally or more impaired for replication in vitro, compared with the ORF63 mutant, is similar to that of animals latently infected with parental VZV. Examination of dorsal root ganglia 3 days after infection showed high levels of VZV DNA in animals infected with either ORF63 mutant or parental virus; however, by days 6 and 10 after infection, the level of viral DNA in animals infected with the ORF63 mutant was significantly lower than that in animals infected with parental virus. Thus, ORF63 is not required for VZV to enter ganglia but is the first VZV gene shown to be critical for establishment of latency. Since the present vaccine can reactivate and cause shingles, a VZV vaccine based on the ORF63 mutant virus might be safer.

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Neuronal Subtype and Satellite Cell Tropism Are Determinants of Varicella-Zoster Virus Virulence in Human Dorsal Root Ganglia Xenografts In Vivo

PLoS Pathogens ◽

10.1371/journal.ppat.1004989 ◽

2015 ◽

Vol 11 (6) ◽

pp. e1004989 ◽

Cited By ~ 19

Author(s):

Leigh Zerboni ◽

Ann Arvin

Keyword(s):

Varicella Zoster Virus ◽

Satellite Cell ◽

Dorsal Root Ganglia ◽

Dorsal Root ◽

Cell Tropism ◽

Varicella Zoster ◽

Neuronal Subtype

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Latency In Vitro of Varicella-Zoster Virus in Cells Derived from Human Fetal Dorsal Root Ganglia

Pediatric Research ◽

10.1203/00006450-199212000-00016 ◽

1992 ◽

Vol 32 (6) ◽

pp. 699-703 ◽

Cited By ~ 5

Author(s):

Eli Somekh ◽

Davol G Tedder ◽

Abbas Vafai ◽

José G Assouline ◽

Stephen E Straus ◽

...

Keyword(s):

Varicella Zoster Virus ◽

Dorsal Root Ganglia ◽

Dorsal Root ◽

Varicella Zoster ◽

In Cells

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Typical case: herpes zoster

Revista da Associação Médica Brasileira ◽

10.1590/1806-9282.61.02.114 ◽

2015 ◽

Vol 61 (2) ◽

pp. 114-115

Author(s):

Guilherme Cristianini Baldivia ◽

Gustavo Silveira Graudenz

Keyword(s):

Herpes Zoster ◽

Varicella Zoster Virus ◽

Dorsal Root Ganglia ◽

Causative Agent ◽

Dorsal Root ◽

Typical Case ◽

Varicella Zoster

Summary The varicella zoster virus is the causative agent of herpes zoster and varicella. In herpes zoster, the virus dormant within dorsal root ganglia is reactivated, resulting in painful vesicular lesions overlying an erythematous base.

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