Lessons to be learned from varicella-zoster virus.
Varicella-zoster virus (VZV) is an alphaherpesvirus responsible for two human diseases: chicken pox and shingles. The virus has a respiratory port of entry. After two successive viremias, it reaches the skin where it causes typical lesions. There, it penetrates the peripheral nervous system and it remains latent in dorsal root ganglia. It is still debatable whether VZV persists in neurons or in satellite cells. During latency, VZV expresses a limited set of transcripts of its immediate early (IE) and early (E) genes but no protein has been detected. Mechanisms of reactivation from ganglia have not been identified. However, dysfunction of the cellular immune system appears to be involved in this process. The cell-associated nature of VZV has made it difficult to identify a temporal order of gene expression, but there appears to be a cascade mechanism as for HSV-1. The lack of high titre cell-free virions or recombination mutants has hindered so far the understanding of VZV gene functions. Five genes, ORFs 4, 10, 61, 62, and 63 that encode regulatory proteins could be involved in VZV latency. ORF4p activates gene promoters with basal activities. ORF10p seems to activate the ORF 62 promoter. ORF61p has trans-activating and trans-repressing activities. The major IE protein ORF62p, a virion component, has DNA-binding and regulatory functions, transactivates many VZV promoters and even regulates its own expression. ORF63p is a nuclear IE protein of yet unclear regulatory functions, abundantly expressed very early in infection. We have established an animal model of VZV latency in the rat nervous system, enabling us to study the expression of viral mRNA and protein expression during latency, and yielding results similar to those found in humans. This model is beginning to shed light on the molecular events in VZV persistent infection and on the regulatory mechanisms that maintain the virus in a latent stage in nerve cells.
Rentier
B
B
Department of Microbiology, University of Liège, Belgium. brentier@ulg.ac.be
Piette
J
J
Baudoux
L
L
Debrus
S
S
Defechereux
P
P
Merville
M P
MP
Sadzot-Delvaux
C
C
Schoonbroodt
S
S
D000818:Animals; D002644:Chickenpox / Q000503:physiopathology / Q000821:virology; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000821:virology; D005814:Genes, Viral; D006168:Guinea Pigs; D006562:Herpes Zoster / Q000503:physiopathology / Q000821:virology; D014645:Herpesvirus 3, Human / Q000302:isolation & purification / Q000472:pathogenicity* / Q000502:physiology*; D006801:Humans; D009474:Neurons / Q000821:virology; D016366:Open Reading Frames; D010146:Pain; D051381:Rats; D014764:Viral Proteins / Q000096:biosynthesis; D017735:Virus Latency
D014764:Viral Proteins