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Differential methylation of Epstein-Barr virus latency promoters facilitates viral persistence in healthy seropositive individuals.
J Virol. 1999 Dec; 73(12):9959-68.JV

Abstract

Epstein-Barr virus (EBV) establishes a life-long infection in humans, with distinct viral latency programs predominating during acute and chronic phases of infection. Only a subset of the EBV latency-associated antigens present during the acute phase of EBV infection are expressed in the latently infected memory B cells that serve as the long-term EBV reservoir. Since the EBV immortalization program elicits a potent cellular immune response, downregulation of viral gene expression in the long-term latency reservoir is likely to facilitate evasion of the immune response and persistence of EBV in the immunocompetent host. Tissue culture and tumor models of restricted EBV latency have consistently demonstrated a critical role for methylation of the viral genome in maintaining the restricted pattern of latency-associated gene expression. Here we extend these observations to demonstrate that the EBV genomes in the memory B-cell reservoir are also heavily and discretely methylated. This analysis reveals that methylation of the viral genome is a normal aspect of EBV infection in healthy immunocompetent individuals and is not restricted to the development of EBV-associated tumors. In addition, the pattern of methylation very likely accounts for the observed inhibition of the EBV immortalization program and the establishment and maintenance of a restricted latency program. Thus, EBV appears to be the first example of a parasite that usurps the host cell-directed methylation system to regulate pathogen gene expression and thereby establish a chronic infection.

Authors+Show Affiliations

Department of Pathology, Washington University School of Medicine, St. Louis, Missouri, USA.No affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

10559309

Citation

Paulson, E J., and S H. Speck. "Differential Methylation of Epstein-Barr Virus Latency Promoters Facilitates Viral Persistence in Healthy Seropositive Individuals." Journal of Virology, vol. 73, no. 12, 1999, pp. 9959-68.
Paulson EJ, Speck SH. Differential methylation of Epstein-Barr virus latency promoters facilitates viral persistence in healthy seropositive individuals. J Virol. 1999;73(12):9959-68.
Paulson, E. J., & Speck, S. H. (1999). Differential methylation of Epstein-Barr virus latency promoters facilitates viral persistence in healthy seropositive individuals. Journal of Virology, 73(12), 9959-68.
Paulson EJ, Speck SH. Differential Methylation of Epstein-Barr Virus Latency Promoters Facilitates Viral Persistence in Healthy Seropositive Individuals. J Virol. 1999;73(12):9959-68. PubMed PMID: 10559309.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Differential methylation of Epstein-Barr virus latency promoters facilitates viral persistence in healthy seropositive individuals. AU - Paulson,E J, AU - Speck,S H, PY - 1999/11/13/pubmed PY - 1999/11/13/medline PY - 1999/11/13/entrez SP - 9959 EP - 68 JF - Journal of virology JO - J. Virol. VL - 73 IS - 12 N2 - Epstein-Barr virus (EBV) establishes a life-long infection in humans, with distinct viral latency programs predominating during acute and chronic phases of infection. Only a subset of the EBV latency-associated antigens present during the acute phase of EBV infection are expressed in the latently infected memory B cells that serve as the long-term EBV reservoir. Since the EBV immortalization program elicits a potent cellular immune response, downregulation of viral gene expression in the long-term latency reservoir is likely to facilitate evasion of the immune response and persistence of EBV in the immunocompetent host. Tissue culture and tumor models of restricted EBV latency have consistently demonstrated a critical role for methylation of the viral genome in maintaining the restricted pattern of latency-associated gene expression. Here we extend these observations to demonstrate that the EBV genomes in the memory B-cell reservoir are also heavily and discretely methylated. This analysis reveals that methylation of the viral genome is a normal aspect of EBV infection in healthy immunocompetent individuals and is not restricted to the development of EBV-associated tumors. In addition, the pattern of methylation very likely accounts for the observed inhibition of the EBV immortalization program and the establishment and maintenance of a restricted latency program. Thus, EBV appears to be the first example of a parasite that usurps the host cell-directed methylation system to regulate pathogen gene expression and thereby establish a chronic infection. SN - 0022-538X UR - https://www.unboundmedicine.com/medline/citation/10559309/Differential_methylation_of_Epstein_Barr_virus_latency_promoters_facilitates_viral_persistence_in_healthy_seropositive_individuals_ L2 - http://jvi.asm.org/cgi/pmidlookup?view=long&pmid=10559309 DB - PRIME DP - Unbound Medicine ER -