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37 - VZV: pathogenesis and the disease consequences of primary infection

from Part III - Pathogenesis, clinical disease, host response, and epidemiology: VZU

Published online by Cambridge University Press:  24 December 2009

By
Jennifer Moffat ,
Chia-Chi Ku ,
Leigh Zerboni ,
Marvin Sommer  and
Ann Arvin
Edited by
Ann Arvin ,
Gabriella Campadelli-Fiume ,
Edward Mocarski ,
Patrick S. Moore ,
Bernard Roizman ,
Richard Whitley  and
Koichi Yamanishi
Jennifer Moffat
Affiliation:
Suny Upstate Medical University, Syracuse, NY, USA
Chia-Chi Ku
Affiliation:
Stanford University, CA, USA
Leigh Zerboni
Affiliation:
Stanford University, CA, USA
Marvin Sommer
Affiliation:
Stanford University, CA, USA
Ann Arvin
Affiliation:
Stanford University, CA, USA
Ann Arvin
Affiliation:
Stanford University, California
Gabriella Campadelli-Fiume
Affiliation:
Università degli Studi, Bologna, Italy
Edward Mocarski
Affiliation:
Emory University, Atlanta
Patrick S. Moore
Affiliation:
University of Pittsburgh
Bernard Roizman
Affiliation:
University of Chicago
Richard Whitley
Affiliation:
University of Alabama, Birmingham
Koichi Yamanishi
Affiliation:
University of Osaka, Japan
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Summary

Introduction

VZV is a human alphaherpesvirus that causes varicella (chickenpox) as the primary infection and establishes latency in sensory ganglia. VZV reactivation results in herpes zoster (shingles). During the course of varicella and zoster, VZV infects differentiated human cells that exist within unique tissue microenvironments in humans. The tropism of VZV for skin is the most obvious clinical manifestation of VZV infection, producing the vesicular cutaneous lesions that are associated with varicella and zoster. The site of initial VZV infection in naïve hosts is thought to be mucosal epithelial cells of the upper respiratory tract. Entry is presumed to follow inoculation of the respiratory epithelium with infectious virus transmitted by aerosolized respiratory droplets or by contact with virus in varicella or zoster skin lesions (Arvin, 2001a; Grose, 1981). VZV in respiratory or conjunctival mucosal cells has the opportunity to interact with and infect local immune system cells and those in adjacent lymphoid tissues. Trafficking of infected peripheral blood mononuclear cells (PBMC), which appear to be predominantly T-cells, to the skin is thought to give rise to crops of cutaneous vesicles. Skin lesions contain VZV material associated with necrotic debris and, unlike virus grown in vitro, cell-free, infectious particles are detected in vesicular fluid (Williams et al., 1962). The life cycle of VZV is completed upon its transmission to a susceptible host from an individual with varicella, or it can be postponed for decades by establishing latency in neurons and transmitting to future generations during episodes of zoster.

Type
Chapter
Information
Human Herpesviruses
Biology, Therapy, and Immunoprophylaxis
 , pp. 675 - 688
Publisher: Cambridge University Press
Print publication year: 2007

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References

Annunziato, P. W., Lungu, O., Panagiotidis, C.et al. (2000). Varicella-zoster virus proteins in skin lesions: implications for a novel role of ORF29p in chickenpox. J. Virol., 74(4), 2005–2010.CrossRefGoogle ScholarPubMed
Arvin, A. M. (2001a). Varicella-zoster virus. 4th edn. In Fields Virology, Knipe, D. M., and Howley, P. M., eds., Vol. 2, pp. 2731–2768. Philadelphia: Lippincott-Raven.Google Scholar
Arvin, A. M. (2001b). Varicella-zoster virus: molecular virology and virus–host interactions. Curr. Opin. Microbiol., 4(4), 442–449.CrossRefGoogle Scholar
Asano, Y., Itakura, N., Kajita, Y.et al. (1990). Severity of viremia and clinical findings in children with varicella. J. Infect. Dis., 161(6), 1095–1098.CrossRefGoogle ScholarPubMed
Baiker, A., Bagowski, C., Ito, H.et al. (2004). The immediate-early 63 protein of Varicella-Zoster virus: analysis of functional domains required for replication in vitro and for T-cell and skin tropism in the SCIDhu model in vivo. J. Virol., 78(3), 1181–1194.CrossRefGoogle ScholarPubMed
Berarducci, B., Ikoma, M., Stamatis, S., Sommer, M., Grose, C. and Arvin, A. M. (2006). Essential functions of the unique N-terminal region of the Varicella-zoster virus glycoprotein E ectodomain in viral replication and in the pathogenesis of skin infection, J. Virol, in press.CrossRef
Besser, J., Ikoma, M., Fabel, K.et al. (2004). Differential requirement for cell fusion and virion formation in the pathogenesis of varicella-zoster virus infection in skin and T cells. J. Virol., 78(23), 13293–13305.CrossRefGoogle ScholarPubMed
Besser, J., Sommer, M. H., Zerboni, L.et al. (2003). Differentiation of varicella-zoster virus ORF47 protein kinase and IE62 protein binding domains and their contributions to replication in human skin xenografts in the SCID-hu mouse. J. Virol., 77(10), 5964–5974.CrossRefGoogle ScholarPubMed
Che, X., Zerboni, L., Sommer, M. H., and Arvin, A. M. (2006). Varicella-zoster virus open reading frame 10 is a virulence determinant in skin cells but not in T-cellsin vivo. J. Virol., 7, 3238–3248.CrossRefGoogle Scholar
Cohen, J. I. and Nguyen, H. (1997). Varicella-zoster virus glycoprotein I is essential for growth of virus in Vero cells. J. Virol., 71(9), 6913–6920.Google ScholarPubMed
Cohen, J. I. and Seidel, K. E. (1993). Generation of varicella-zoster virus (VZV) and viral mutants from cosmid DNAs: VZV thymidylate synthetase is not essential for replication in vitro. Proc. Natl Acad. Sci. USA, 90, 7376–7380.CrossRefGoogle Scholar
Cohen, J. I. and Straus, S. E. (2001). Varicella-zoster virus and its replication. 4th edn. In Fields Virology, Knipe, D. M., and Howley, P. M., eds., Vol. 2, pp. 2707–2730. Philadelphia: Lippincott-Raven.Google Scholar
Cohen, J. I., Cox, E., Pesnicak, L., Srinivas, S., and Krogmann, T. (2004). The varicella-zoster virus open reading frame 63 latency-associated protein is critical for establishment of latency. J. Virol., 78(21), 11833–11840.CrossRefGoogle ScholarPubMed
Cole, N. L. and Grose, C. (2003). Membrane fusion mediated by herpesvirus glycoproteins: the paradigm of varicella-zoster virus. Rev. Med. Virol., 13(4), 207–222.CrossRefGoogle ScholarPubMed
Davison, A. J. and Scott, J. E. (1986). The complete DNA sequence of varicella-zoster virus. J. Gen. Virol., 67, 1759–1816.CrossRefGoogle ScholarPubMed
Dunkle, L. M., Arvin, A. M., Whitley, R. J.et al. (1991). A controlled trial of acyclovir for chickenpox in normal children. N. Engl. J. Med., 325(22), 1539–1544.CrossRefGoogle ScholarPubMed
Dworsky, M., Whitley, R., and Alford, C. (1980). Herpes zoster in early infancy. Am. J. Dis. Child., 134(6), 618–619.Google ScholarPubMed
Enders, G., Miller, E., Cradock-Watson, J., Bolley, I., and Ridehalgh, M. (1994). Consequences of varicella and herpes zoster in pregnancy: prospective study of 1739 cases. Lancet, 343(8912), 1548–1551.CrossRefGoogle ScholarPubMed
Feldhoff, C. M., Balfour, H. H. Jr., Simmons, R. L., Najarian, J. S., and Mauer, S. M. (1981). Varicella in children with renal transplants. J. Pediatr., 98(1), 25–31.CrossRefGoogle ScholarPubMed
Feldman, S. and Lott, L. (1987). Varicella in children with cancer: impact of antiviral therapy and prophylaxis. Pediatrics, 80(4), 465–472.Google ScholarPubMed
Gershon, A. A., Steinberg, S., and Silber, R. (1978). Varicella-zoster viremia. J. Pediatr., 92(6), 1033–1034.CrossRefGoogle ScholarPubMed
Gershon, A., Steinberg, S., Greenberg, S., and Taber, L. (1980). Varicella-zoster-associated encephalitis: detection of specific antibody in cerebrospinal fluid. J. Clin. Microbiol., 12(6), 764–767.Google ScholarPubMed
Grose, C. (1981). Variation on a theme by Fenner: the pathogenesis of chicken pox. Pediatrics, 68, 735–737.Google Scholar
He, H., Boucaud, D., Hay, J., and Ruyechan, W. T. (2001). Cis and trans elements regulating expression of the varicella zoster virus gI gene. Arch. Virol. Suppl.(17), 57–70.CrossRef
Heineman, T. C., Seidel, K., and Cohen, J. I. (1996). The varicella-zoster virus ORF66 protein induces kinase activity and is dispensable for viral replication. J. Virol., 70(10), 7312–7317.Google ScholarPubMed
Ito, H., Sommer, M. H., Zerboni, L.et al. (2003). Promoter sequences of varicella-zoster virus glycoprotein I targeted by cellular transactivating factors Sp1 and USF determine virulence in skin and T cells in SCIDhu mice in vivo. J. Virol., 77(1), 489–498.CrossRefGoogle Scholar
Jackson, M. A., Burry, V. F., and Olson, L. C. (1992). Complications of varicella requiring hospitalization in previously healthy children. Pediatr. Infect. Dis. J., 11(6), 441–445.CrossRefGoogle ScholarPubMed
Johnson, R. and Milbourn, P. E. (1970). Central nervous system manifestations of chickenpox. Can. Med. Assoc. J., 102(8), 831–834.Google ScholarPubMed
Jones, J. O. and Arvin, A. M. (2006). Inhibition of the NF-κB pathway by varicella-zoster virus in vitro and in human epidermal cells in vivo. J. Virol., 80(11), 5113–5124.CrossRefGoogle ScholarPubMed
Jura, E., Chadwick, E. G., Josephs, S. H.et al. (1989). Varicella-zoster virus infections in children infected with human immunodeficiency virus. Pediatr. Infect. Dis. J., 8(9), 586–590.CrossRefGoogle ScholarPubMed
Kelley, R., Mancao, M., Lee, F., Sawyer, M., Nahmias, A., and Nesheim, S. (1994). Varicella in children with perinatally acquired human immunodeficiency virus infection. J. Pediatr., 124(2), 271–273.CrossRefGoogle ScholarPubMed
Kemble, G. W., Annunziato, 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(23), 11311–11321.CrossRefGoogle ScholarPubMed
Kinchington, P. R., Hougland, J. K., Arvin, A. M., Ruyechan, W. T., and Hay, J. (1992). The varicella-zoster virus immediate-early protein IE62 is a major component of virus particles. J. Virol., 66(1), 359–366.Google ScholarPubMed
Kinchington, P. R., Vergnes, J. P., Defechereux, P., Piette, J., and Turse, S. E. (1994). Transcriptional mapping of the varicella-zoster virus regulatory genes encoding open reading frames 4 and 63. J. Virol., 68(6), 3570–3581.Google ScholarPubMed
Koropchak, C. M., Diaz, P. S., and Arvin, A. M. (1989). Investigation of varicella-zoster virus infection of lymphocytes by in situ hybridization. J. Virol., 63, 2392–2395.Google ScholarPubMed
Koropchak, C. M., Graham, G., Palmer, J.et al. (1991). Investigation of varicella-zoster virus infection by polymerase chain reaction in the immunocompetent host with acute varicella. J. Infect. Dis., 163, 1016–1022.CrossRefGoogle ScholarPubMed
Krugman, S., Goodrich, C. H., and Ward, R. (1957). Primary varicella pneumonia. N. Engl. J. Med., 257(18), 843–848.CrossRefGoogle ScholarPubMed
Ku, C. C., Padilla, J. A., Grose, C., Butcher, E. C., and Arvin, A. M. (2002). Tropism of varicella-zoster virus for human tonsillar CD4(+) T lymphocytes that express activation, memory, and skin homing markers. J. Virol., 76(22), 11425–11433.CrossRefGoogle ScholarPubMed
Ku, C. C., Zerboni, L., Ito, H., Graham, B. S., Wallace, M., and Arvin, A. M. (2004). Varicella-zoster virus transfer to skin by T Cells and modulation of viral replication by epidermal cell interferon-alpha. J. Exp. Med., 200(7), 917–925.CrossRefGoogle Scholar
Leisenfelder, S. A. and Moffat, J. F. (2006). Varicella-zoster virus infection of human foreskin fibroblast cells results in atypical cyclin expression and cyclin-dependent kinase activity. J. Virol., 80(11), 5577–5587.CrossRefGoogle ScholarPubMed
Liesegang, T. J. (1991). Diagnosis and therapy of herpes zoster ophthalmicus. Ophthalmology, 98(8), 1216–1229.CrossRefGoogle ScholarPubMed
Mallory, S., Sommer, M., and Arvin, A. M. (1997). Mutational analysis of the role of glycoprotein I in varicella-zoster virus replication and its effects on glycoprotein E conformation and trafficking. J. Virol., 71(11), 8279–8288.Google Scholar
Mo, C., Suen, J., Sommer, M., and Arvin, A. (1999). Characterization of Varicella-Zoster virus glycoprotein K (open reading frame 5) and its role in virus growth. J. Virol., 73(5), 4197–4207.Google ScholarPubMed
Mo, C., Lee, J., Sommer, M., Grose, C., and Arvin, A. M. (2002). The requirement of varicella zoster virus glycoprotein E (gE) for viral replication and effects of glycoprotein I on gE in melanoma cells. Virology, 304(2), 176–186.CrossRefGoogle ScholarPubMed
Moffat, J., Ito, H., Sommer, M., Taylor, S., and Arvin, A. M. (2002). Glycoprotein I of varicella-zoster virus is required for viral replication in skin and T cells. J. Virol., 76(16), 8468–8471.CrossRefGoogle ScholarPubMed
Moffat, J., Mo, C., Cheng, J. J.et al. (2004a). Functions of the C-terminal domain of varicella-zoster virus glycoprotein E in viral replication in vitro and skin and T-cell tropism in vivo. J. Virol., 78(22), 12406–12415.CrossRefGoogle Scholar
Moffat, J. F., McMichael, M. A., Leisenfelder, S. A., and Taylor, S. L. (2004b). Viral and cellular kinases are potential antiviral targets and have a central role in varicella zoster virus pathogenesis. Biochim. Biophys. Acta., 1697(1–2), 225–231.CrossRefGoogle Scholar
Moffat, J. F., Stein, M. D., Kaneshima, H., and Arvin, A. M. (1995). Tropism of varicella-zoster virus for human CD4+ and CD8+ T lymphocytes and epidermal cells in SCID-hu mice. J. Virol., 69(9), 5236–5242.Google ScholarPubMed
Moffat, J. F., Zerboni, L., Sommer, M. H.et al. (1998). The ORF47 and ORF66 putative protein kinases of varicella-zoster virus determine tropism for human T cells and skin in the SCID-hu mouse. Proc. Natl Acad. Sci. USA, 95(20), 11969–11974.CrossRefGoogle Scholar
Myers, M. G. (1979). Viremia caused by varicella-zoster virus: association with malignant progressive varicella. J. Infect. Dis., 140, 229–233.CrossRefGoogle ScholarPubMed
Niizuma, T., Zerboni, L., Sommer, M. H., Ito, H., Hinchliffe, S., and Arvin, A. M. (2003). Construction of varicella-zoster virus recombinants from parent oka cosmids and demonstration that ORF65 protein is dispensable for infection of human skin and T cells in the SCID-hu mouse model. J. Virol., 77(10), 6062–6065.CrossRefGoogle Scholar
Olashaw, N. and Pledger, W. J. (2002). Paradigms of growth control: relation to Cdk activation. Sci. STKE, 2002(134), RE7.Google ScholarPubMed
Ozaki, T., Ichikawa, T., Matsui, Y.et al. (1986). Lymphocyte-associated viremia in varicella. J. Med. Virol., 19, 249–253.CrossRefGoogle ScholarPubMed
Pastuszak, A. L., Levy, M., Schick, B.et al. (1994). Outcome after maternal varicella infection in the first 20 weeks of pregnancy. N. Engl. J. Med., 330(13), 901–905.CrossRefGoogle ScholarPubMed
Peters, A. C., Versteeg, J., Lindeman, J., and Bots, G. T. (1978). Varicella and acute cerebellar ataxia. Arch. Neurol., 35(11), 769–771.CrossRefGoogle ScholarPubMed
Preblud, S. R., Bregman, D. J., and Vernon, L. L. (1985). Deaths from varicella in infants. Pediatr. Infect. Dis., 4(5), 503–507.CrossRefGoogle ScholarPubMed
Sato, B., Ito, H., Hinchliffe, S., Sommer, M. H., Zerboni, L., and Arvin, A. M. (2003a). Mutational analysis of open reading frames 62 and 71, encoding the varicella-zoster virus immediate-early transactivating protein, IE62, and effects on replication in vitro and in skin xenografts in the SCID-hu mouse in vivo. J. Virol., 77(10), 5607–5620.CrossRefGoogle Scholar
Sato, B., Sommer, M., Ito, H., and Arvin, A. M. (2003b). Requirement of varicella-zoster virus immediate-early 4 protein for viral replication. J. Virol., 77(22), 12369–12372.CrossRefGoogle Scholar
Schaap, A., Fortin, J. F., Sommer, M.et al. (2005). T-cell tropism and the role of ORF66 protein in the pathogenesis of varicella-zoster virus infection. J. Virol., 79, 12921–33.CrossRefGoogle ScholarPubMed
Sommer, M. H., Zagha, E., Serrano, O. K.et al. (2001). Mutational analysis of the repeated open reading frames, ORFs 63 and 70 and ORFs 64 and 69, of varicella-zoster virus. J. Virol., 75(17), 8224–8239.CrossRefGoogle ScholarPubMed
Soong, W., Schultz, J. C., Patera, A. C., Sommer, M. H., and Cohen, J. I. (2000). Infection of human T lymphocytes with varicella-zoster virus: an analysis with viral mutants and clinical isolates. J. Virol., 74(4), 1864–1870.CrossRefGoogle Scholar
Takahashi, K., Sonoda, S., Higashi, K.et al. (1989). Predominant CD4 T-lymphocyte tropism of human herpesvirus 6-related virus. J. Virol., 63(7), 3161–3163.Google ScholarPubMed
Taylor, S. L., Kinchington, P. R., Brooks, A., and Moffat, J. F. (2004). Roscovitine, a cyclin dependent kinase inhibitor, prevents replication of varicella-zoster virus. J. Virol., 78(6), 2853–2862.CrossRefGoogle ScholarPubMed
Williams, M. G., Almeida, J. D., and Howatson, A. F. (1962). Electron microscope studies on viral skin lesions. Arch. Dermatol., 86, 290–297.CrossRefGoogle ScholarPubMed
Ye, M., Duus, K. M., Peng, J., Price, D. H., and Grose, C. (1999). Varicella-zoster virus Fc receptor component gI is phosphorylated on its endodomain by a cyclin-dependent kinase. J. Virol., 73(2), 1320–1330.Google ScholarPubMed

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