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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
MeSH Review

Virus Latency

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Disease relevance of Virus Latency

  • We present an extensive experimental/computational study of an HIV-1 model vector (LTR-GFP-IRES-Tat) and show that stochastic fluctuations in Tat influence the viral latency decision [1].
  • Oral acyclovir treatment of first-episode genital herpes simplex virus infections is clinically effective, but it does not seem to prevent virus latency or associated recurrent disease [2].
  • Partial sequencing of HIV pol revealed no new drug resistance mutations or discernible evolution, providing evidence for viral latency rather than drug failure [3].
  • Acyclovir provided significant antiviral and clinical efficacy without toxicity in highly immunosuppressed patients but had no effect on virus latency [4].
  • Elucidation of the genetic mechanism responsible for the EBNA-1-restricted program of EBV latency is an essential step in understanding control of viral latency in EBV-associated tumors [5].

High impact information on Virus Latency

  • Surprisingly, distinct neuronal subsets require different CD8 effector mechanisms to maintain viral latency, with some requiring IFN-gamma and others requiring lytic granules (LG) [6].
  • These data suggest a key role of IRF-1 in the early phase of viral replication and/or during viral reactivation from latency, when viral transactivators are absent or present at very low levels, and suggest that the interplay between IRF-1 and IRF-8 may play a key role in virus latency [7].
  • Cellular regulation of BZLF1 transcription is therefore thought to play a key role in regulating the stringency of viral latency [8].
  • Here we show that, unexpectedly, expression of another viral immediate-early protein, BRLF1, can disrupt viral latency in an epithelial cell-specific fashion [8].
  • Inspection of Qp revealed that it is a TATA-less promoter whose architecture is similar to the promoters of housekeeping genes, suggesting that Qp may be a default promoter which ensures EBNA-1 expression in cells that cannot run the full viral latency program [5].

Chemical compound and disease context of Virus Latency


Biological context of Virus Latency


Anatomical context of Virus Latency


Associations of Virus Latency with chemical compounds


Gene context of Virus Latency

  • Effect of DNA-binding drugs on early growth response factor-1 and TATA box-binding protein complex formation with the herpes simplex virus latency promoter [24].
  • These results provide evidence for IL-18 expression in response to a viral latency protein and suggest that IL-18 may play an important role as an endogenous inducer of IFN-gamma expression, thereby contributing to tumor regression [25].
  • During viral latency of more than two months, ET secretion, preproendothelin-1 (PPET-1) mRNA, and endothelin receptor subtype A (ETAR) mRNA within the cells remained suppressed [26].
  • As the M phi may be involved in MCMV latency, IFN gamma- and TNF alpha-dependent M phi activation during primary infection may be relevant to establishment of viral latency [27].
  • BHRF1 transcripts were found to be generated by the C or W promoter (associated with viral latency) and/or by the H promoter (associated with the virus lytic cycle) [28].

Analytical, diagnostic and therapeutic context of Virus Latency


  1. Stochastic gene expression in a lentiviral positive-feedback loop: HIV-1 Tat fluctuations drive phenotypic diversity. Weinberger, L.S., Burnett, J.C., Toettcher, J.E., Arkin, A.P., Schaffer, D.V. Cell (2005) [Pubmed]
  2. Treatment of first episodes of genital herpes simplex virus infection with oral acyclovir. A randomized double-blind controlled trial in normal subjects. Bryson, Y.J., Dillon, M., Lovett, M., Acuna, G., Taylor, S., Cherry, J.D., Johnson, B.L., Wiesmeier, E., Growdon, W., Creagh-Kirk, T., Keeney, R. N. Engl. J. Med. (1983) [Pubmed]
  3. Recovery of replication-competent HIV despite prolonged suppression of plasma viremia. Wong, J.K., Hezareh, M., Günthard, H.F., Havlir, D.V., Ignacio, C.C., Spina, C.A., Richman, D.D. Science (1997) [Pubmed]
  4. Intravenous acyclovir to treat mucocutaneous herpes simplex virus infection after marrow transplantation: a double-blind trial. Wade, J.C., Newton, B., McLaren, C., Flournoy, N., Keeney, R.E., Meyers, J.D. Ann. Intern. Med. (1982) [Pubmed]
  5. Redefining the Epstein-Barr virus-encoded nuclear antigen EBNA-1 gene promoter and transcription initiation site in group I Burkitt lymphoma cell lines. Schaefer, B.C., Strominger, J.L., Speck, S.H. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  6. Sensory neurons regulate the effector functions of CD8(+) T cells in controlling HSV-1 latency ex vivo. Prabhakaran, K., Sheridan, B.S., Kinchington, P.R., Khanna, K.M., Decman, V., Lathrop, K., Hendricks, R.L. Immunity (2005) [Pubmed]
  7. Modulation of human immunodeficiency virus 1 replication by interferon regulatory factors. Sgarbanti, M., Borsetti, A., Moscufo, N., Bellocchi, M.C., Ridolfi, B., Nappi, F., Marsili, G., Marziali, G., Coccia, E.M., Ensoli, B., Battistini, A. J. Exp. Med. (2002) [Pubmed]
  8. Epstein-Barr viral latency is disrupted by the immediate-early BRLF1 protein through a cell-specific mechanism. Zalani, S., Holley-Guthrie, E., Kenney, S. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  9. N-linked oligosaccharides on herpes simplex virus glycoprotein gD are not essential for establishment of viral latency or reactivation in the mouse eye model. Tal-Singer, R., Eisenberg, R.J., Valyi-Nagy, T., Fraser, N.W., Cohen, G.H. Virology (1994) [Pubmed]
  10. Establishment of herpes simplex virus latency in vitro with cycloheximide. Shiraki, K., Rapp, F. J. Gen. Virol. (1986) [Pubmed]
  11. Functional and physical interactions between the Epstein-Barr virus (EBV) proteins BZLF1 and BMRF1: Effects on EBV transcription and lytic replication. Zhang, Q., Hong, Y., Dorsky, D., Holley-Guthrie, E., Zalani, S., Elshiekh, N.A., Kiehl, A., Le, T., Kenney, S. J. Virol. (1996) [Pubmed]
  12. Nasopharyngeal carcinoma cell line (C666-1) consistently harbouring Epstein-Barr virus. Cheung, S.T., Huang, D.P., Hui, A.B., Lo, K.W., Ko, C.W., Tsang, Y.S., Wong, N., Whitney, B.M., Lee, J.C. Int. J. Cancer (1999) [Pubmed]
  13. Photochemical deamination and demethylation of 5-methylcytosine. Privat, E., Sowers, L.C. Chem. Res. Toxicol. (1996) [Pubmed]
  14. Interleukin-10 inhibits initial reverse transcription of human immunodeficiency virus type 1 and mediates a virostatic latent state in primary blood-derived human macrophages in vitro. Montaner, L.J., Griffin, P., Gordon, S. J. Gen. Virol. (1994) [Pubmed]
  15. Epstein-Barr virus gene expression in human breast cancer: protagonist or passenger? Xue, S.A., Lampert, I.A., Haldane, J.S., Bridger, J.E., Griffin, B.E. Br. J. Cancer (2003) [Pubmed]
  16. Differentiation-associated expression of the Epstein-Barr virus BZLF1 transactivator protein in oral hairy leukoplakia. Young, L.S., Lau, R., Rowe, M., Niedobitek, G., Packham, G., Shanahan, F., Rowe, D.T., Greenspan, D., Greenspan, J.S., Rickinson, A.B. J. Virol. (1991) [Pubmed]
  17. NF-kappaB inhibits gammaherpesvirus lytic replication. Brown, H.J., Song, M.J., Deng, H., Wu, T.T., Cheng, G., Sun, R. J. Virol. (2003) [Pubmed]
  18. Marked, transient inhibition of expression of the Epstein-Barr virus latent membrane protein gene in Burkitt's lymphoma cell lines by electroporation. Gahn, T.A., Sugden, B. J. Virol. (1993) [Pubmed]
  19. Acylovir in oral and ganglionic herpes simplex virus infections. Park, N.H., Pavan-Langston, D., McLean, S.L. J. Infect. Dis. (1979) [Pubmed]
  20. Murine gammaherpesvirus 68 bcl-2 homologue contributes to latency establishment in vivo. de Lima, B.D., May, J.S., Marques, S., Simas, J.P., Stevenson, P.G. J. Gen. Virol. (2005) [Pubmed]
  21. Acyclovir prophylaxis against herpes simplex virus infection in patients with leukemia. A randomized, double-blind, placebo-controlled study. Saral, R., Ambinder, R.F., Burns, W.H., Angelopulos, C.M., Griffin, D.E., Burke, P.J., Lietman, P.S. Ann. Intern. Med. (1983) [Pubmed]
  22. Inhibition of HIV activation in latently infected cells by flavonoid compounds. Critchfield, J.W., Butera, S.T., Folks, T.M. AIDS Res. Hum. Retroviruses (1996) [Pubmed]
  23. Enhanced in vitro reactivation of latent herpes simplex virus from neural and peripheral tissues with hexamethylenebisacetamide. Bernstein, D.I., Kappes, J.C. Arch. Virol. (1988) [Pubmed]
  24. Effect of DNA-binding drugs on early growth response factor-1 and TATA box-binding protein complex formation with the herpes simplex virus latency promoter. Chiang, S.Y., Welch, J.J., Rauscher, F.J., Beerman, T.A. J. Biol. Chem. (1996) [Pubmed]
  25. Interleukin-18 expression induced by Epstein-Barr virus-infected cells. Yao, L., Setsuda, J., Sgadari, C., Cherney, B., Tosato, G. J. Leukoc. Biol. (2001) [Pubmed]
  26. Suppression of endothelin system in Vero cells latently infected with influenza virus B/Lee/40. Hayase, Y., Tobita, K. Arch. Virol. (1999) [Pubmed]
  27. The T-cell-independent role of gamma interferon and tumor necrosis factor alpha in macrophage activation during murine cytomegalovirus and herpes simplex virus infections. Heise, M.T., Virgin, H.W. J. Virol. (1995) [Pubmed]
  28. BHRF1, the Epstein-Barr virus (EBV) homologue of the BCL-2 protooncogene, is transcribed in EBV-associated B-cell lymphomas and in reactive lymphocytes. Oudejans, J.J., van den Brule, A.J., Jiwa, N.M., de Bruin, P.C., Ossenkoppele, G.J., van der Valk, P., Walboomers, J.M., Meijer, C.J. Blood (1995) [Pubmed]
  29. Natural history of murine gamma-herpesvirus infection. Nash, A.A., Dutia, B.M., Stewart, J.P., Davison, A.J. Philos. Trans. R. Soc. Lond., B, Biol. Sci. (2001) [Pubmed]
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