Abstract
Varicella zoster virus (VZV) establishes latency in neurons of human peripheral ganglia where the virus genome is most likely maintained as a circular episome bound to histones. There is considerable variability among individuals in the number of latent VZV DNA copies. The VZV DNA burden does not appear to exceed that of herpes simplex type 1 (HSV-1). Expression of VZV genes during latency is highly restricted and is regulated epigenetically. Of the VZV open reading frames (ORFs) that have been analyzed for transcription during latency using cDNA sequencing, only ORFs 21, 29, 62, 63, and 66 have been detected. VZV ORF 63 is the most frequently and abundantly transcribed VZV gene detected in human ganglia during latency, suggesting a critical role for this gene in maintaining the latent state and perhaps the early stages of virus reactivation. The inconsistent detection and low abundance of other VZV transcripts suggest that these genes play secondary roles in latency or possibly reflect a subpopulation of neurons undergoing VZV reactivation. New technologies, such as GeXPS multiplex PCR, have the sensitivity to detect multiple low abundance transcripts and thus provide a means to elucidate the entire VZV transcriptome during latency.
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Abbreviations
- ChIP:
-
Chromatin immunoprecipitation
- DRG:
-
Dorsal root ganglia
- HSV:
-
Herpes simplex virus
- IHC:
-
Immunohistochemistry
- LCM:
-
Laser capture microdissection
- miRNA:
-
MicroRNA
- ORF:
-
Open reading frame
- qRT-PCR:
-
Quantitative reverse transcriptase-PCR
- RT-PCR:
-
Reverse transcriptase-PCR
- TG:
-
Trigeminal ganglia
- VZV:
-
Varicella zoster virus
References
Arvin A (1996) Varicella-zoster virus. Clin Microbiol Rev 9:361–381
Chaudhuri V, Sommer M, Rajamani J et al (2008) Functions of varicella-zoster virus ORF23 capsid protein in viral replication and the pathogenesis of skin infection. J Virol 82:10231–10246
Clarke P, Beer T, Cohrs R et al (1995) Configuration of latent varicella-zoster virus DNA. J Virol 69:8151–8154
Cohrs RJ, Gilden DH (2003) Varicella zoster virus transcription in latently infected ganglia. Anticancer Res 23:2063–2070
Cohrs RJ, Gilden DH (2007) Prevalence and abundance of latently transcribed varicella-zoster virus genes in human ganglia. J Virol 81:2950–2956
Cohrs RJ, Srock K, Barbour MB et al (1994) Varicella-zoster virus (VZV) transcription during latency in human ganglia: construction of a cDNA library from latently infected human trigeminal ganglia and detection of a vzv transcript. J Virol 68:7900–7908
Cohrs RJ, Barbour M, Gilden DH (1996) Varicella-zoster virus (VZV) transcription during latency in human ganglia: detection of transcripts mapping to genes 21, 29, 62, and 63 in cDNA library enriched for VZV RNA. J Virol 70:2789–2796
Cohrs RJ, Randall J, Smith J et al (2000) Analysis of individual human trigeminal ganglia for latent herpes simplex virus type 1 and varicella-zoster virus nucleic acids using real-time PCR. J Virol 74:11464–11471
Cohrs RJ, Gilden DH, Kinchington PR et al (2003a) Varicella-zoster virus gene 66 transcription and translation in latently infected human ganglia. J Virol 77:6660–6665
Cohrs RJ, Hurley MP, Gilden DH (2003b) Array analysis of viral gene transcription during lytic infection of cells in tissue culture with varicella-zoster virus. J Virol 77:11718–11732
Cohrs RJ, LaGuardia JJ, Gilden DH (2005) Distribution of latent herpes simplex virus type-1 and varicella zoster virus DNA in human trigeminal ganglia. Virus Genes 31:223–227
Croen KD, Ostrove JM, Dragovic LJ et al (1988) Patterns of gene expression and sites of latency in human nerve ganglia are different for varicella-zoster and herpes simplex viruses. Proc Natl Acad Sci USA 85:9773–9777
Davison AJ, Scott JE (1986) The complete DNA sequence of varicella-zoster virus. J Gen Virol 67:1759–1816
Dueland AN, Ranneberg-Nilsen T, Degré M (1995) Detection of latent varicella zoster virus DNA and human gene sequences in human trigeminal ganglia by in situ amplification combined with in situ hybridization. Arch Virol 140:2055–2066
Gary L, Gilden DH, Cohrs RJ (2006) Epigenetic regulation of varicella-zoster virus open reading frames 62 and 63 in latently infected human trigeminal ganglia. J Virol 80:4921–4926
Gilden DH, Vafai A, Shtram Y et al (1983) Varicella-zoster virus DNA in human sensory ganglia. Nature 306:478–480
Gilden DH, Rozenman Y, Murray R et al (1987) Detection of varicella-zoster virus nucleic acid in neurons of normal human thoracic ganglia. Ann Neurol 22:377–380
Gilden DH, Gesser R, Smith J et al (2001) Presence of VZV and HSV-1 DNA in human nodose and celiac ganglia. Virus Genes 23:145–147
Grinfeld E, Kennedy PGE (2004) Translation of varicella-zoster virus genes during human ganglionic latency. Virus Genes 29:317–319
Hüfner K, Derfuss T, Herberger S et al (2006) Latency of α-herpes viruses is accompanied by a chronic inflammation in human trigeminal ganglia but not in dorsal root ganglia. J Neuropathol Exp Neurol 65:1022–1030
Hyman RW, Ecker JR, Tenser RB (1983) Varicella-zoster virus RNA in human trigeminal ganglia. Lancet 2:814–816
Kemble GW, Annuziato P, Lungu O et al (2000) Open reading frame S/L of varicella-zoster virus encodes a cytoplasmic protein expressed in infected cells. J Virol 74:11311–11321
Kennedy PG, Grinfeld E, Gow JW (1998) Latent varicella-zoster virus is located predominantly in neurons in human trigeminal ganglia. Proc Natl Acad Sci USA 95:4658–4662
Kennedy PGE, Grinfeld E, Bell JE (2000) Varicella-zoster virus gene expression in latently infected and explanted human ganglia. J Virol 74:11893–11898
Kennedy PGE, Grinfeld E, Craigon M et al (2005) Transcriptomal analysis of varicella-zoster virus infection using long oligonucleotide-based microarrays. J Gen Virol 86:2673–2684
LaGuardia JJ, Cohrs RC, Gilden DH (1999) Prevalence of varicella-zoster virus DNA in dissociated human trigeminal ganglion neurons and nonneuronal cells. J Virol 73:8571–8577
Levin MJ, Cai G-Y, Manchak MD et al (2003) Varicella-zoster virus DNA in cells isolated from human trigeminal ganglia. J Virol 77:6979–6987
Lungu O, Panagiotidis C, Annuziato PW et al (1998) Aberrant intracellular localization of varicella-zoster virus regulatory proteins during latency. Proc Natl Acad Sci USA 95:7080–7085
Mahalingam R, Wellish MC, Dueland AN et al (1992) Localization of herpes simplex virus and varicella zoster virus DNA in human ganglia. Ann Neurol 31:444–448
Mahalingam R, Wellish M, Lederer D et al (1993) Quantitation of latent varicella-zoster virus DNA in human trigeminal ganglia by polymerase chain reaction. J Virol 67:2381–2384
Mahalingam R, Wellish M, Cohrs R et al (1996) Expression of protein encoded by varicella-zoster virus open reading frame 63 in latently infected human ganglionic neurons. Proc Natl Acad Sci USA 93:2122–2124
Mahalingam R, Lasher R, Wellish M et al (1998) Localization of varicella-zoster virus gene 21 protein in virus-infected cells in culture. J Virol 72:6832–6837
Mahalingam R, Kennedy PGE, Gilden DH (1999) The problems of latent varicella zoster virus in human ganglia: precise cell location and viral content. J Neurovirol 5:445–448
Mahalingam R, Traina-Dorge V, Wellish M et al (2007) Simian varicella virus reactivation in cynomologous monkeys. Virology 368:50–59
Meier JL, Holman RP, Croen KD et al (1993) Varicella-zoster virus transcription in human trigeminal ganglia. Virology 193:193–200
Nagel MA, Gilden DH (2007) The protean neurologic manifestations of varicella-zoster virus infection. Cleve Clin J Med 74:489–504
Nagel MA, Gilden D, Shade T et al (2009) Rapid and sensitive detection of 68 unique varicella zoster virus gene transcripts in five multiplex reverse transcription-polymerase chain reactions. J Virol Methods 157:62–68
Peters GA, Tyler SD, Grose C et al (2006) A full-genome phylogenetic analysis of varicella-zoster virus reveals a novel origin of replication-based genotyping scheme and evidence of recombination between major circulating clades. J Virol 80:9850–9860
Pevenstein SR, Williams RK, McChesney D et al (1999) Quantitation of latent varicella-zoster virus and herpes simplex virus genomes in human trigeminal ganglia. J Virol 73:10514–10518
Ross J, Williams M, Cohen JI (1997) Disruption of the varicella-zoster virus dUTPase and the adjacent ORF9A gene results in impaired growth and reduced syncytia formation in vitro. Virology 234:186–195
Theil D, Derfuss T, Paripovic I et al (2003) Latent herpesvirus infection in human trigeminal ganglia causes chronic immune response. Am J Pathol 163:2179–2184
Tyler SD, Peters GA, Grose C et al (2007) Genomic cartography of varicella-zoster virus: a complete genome-based analysis of strain variability with implications for attenuation and phenotypic differences. Virology 359:447–458
Umbach JL, Nagel MA, Cohrs RJ et al (2009) Analysis of human alphaherpesviruses microRNA expression in latently infected human trigeminal ganglia. J Virol 83:10677–10683
Wang K, Lau TY, Morales M et al (2005) Laser-capture microdissection: refining estimates of the quantity and distribution of latent herpes simplex virus 1 and varicella-zoster virus DNA in human trigeminal ganglia at the single-cell level. J Virol 79:14079–14087
Wang F-Z, Weber F, Croce C et al (2008) Human cytomegalovirus infection alters the expression of cellular microRNAspecies that affect its replication. J Virol 82:9065–9074
Acknowledgments
This work was supported in part by Public Health Service grants NS032623 and AG032958 from the National Institutes of Health. The authors thank Dr. Robert Cordery-Cotter and Marina Hoffman for editorial review and Cathy Allen for preparing the manuscript.
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Azarkh, Y., Gilden, D., Cohrs, R.J. (2010). Molecular Characterization of Varicella Zoster Virus in Latently Infected Human Ganglia: Physical State and Abundance of VZV DNA, Quantitation of Viral Transcripts and Detection of VZV-Specific Proteins. In: Abendroth, A., Arvin, A., Moffat, J. (eds) Varicella-zoster Virus. Current Topics in Microbiology and Immunology, vol 342. Springer, Berlin, Heidelberg. https://doi.org/10.1007/82_2009_2
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