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Infection of lymphocytes by a virus that aborts cytotoxic lymphocyte-t activity and establishes persistent infection

Academic Article
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Overview

authors

  • Borrow, P.
  • Tishon, A.
  • Oldstone, Michael

publication date

  • July 1991

journal

  • Journal of Experimental Medicine  Journal

abstract

  • For viruses to establish persistent infections in their hosts, they must possess some mechanism for evading clearance by the immune system. When inoculated into adult immunocompetent mice, wild-type lymphocytic choriomeningitis virus (LCMV ARM) induces a CD8(+)-mediated cytotoxic T lymphocyte (CTL) response that clears the infection within 7-14 d (CTL+ [P-]). By contrast, variant viruses isolated from lymphoid tissues of persistently infected mice fail to induce a CTL response and are thus able to establish a persistent infection in adult mice (CTL- [P+]). This report compares the interaction of CTL+ (P-) and CTL- (P+) viruses with cells of the immune system. Both types of virus initially bind to 2-4% of CD4+ and CD8+ T lymphocytes and replicate within cells of both subsets. The replication of CTL- (P+) and CTL+ (P-) viruses in lymphocytes in vivo is similar for the first 5 d after initiating infection. Thereafter, in mice infected with CTL- (P+) variants, lymphocytes retain viral genetic information, and infectious virus can be recovered throughout the animals' lives. In contrast, when adult mice are infected with wild-type CTL+ (P-) LCMV ARM, virus is not recovered from lymphocytes for greater than 7 d after infection. A CD8(+)-mediated anti-LCMV CTL response is induced in such mice. Clearance of infected lymphocytes is produced by these LCMV-specific CTLs, as shown by their ability to lyse lymphocytes expressing LCMV determinants in vitro and the fact that depletion of CD8+ lymphocytes before infection with CTL+ (P-) viruses results in levels of infected lymphocytes similar to those found in undepleted CTL- (P+)-infected mice. Hence, CTL-mediated lysis of T lymphocytes carrying infectious virus is a critical factor determining whether virus persists or the infection is terminated.

subject areas

  • Animals
  • Antigens, CD4
  • Antigens, CD8
  • Antigens, Differentiation, T-Lymphocyte
  • Cytotoxicity, Immunologic
  • Kinetics
  • Lymphocyte Depletion
  • Lymphocytic Choriomeningitis
  • Lymphocytic choriomeningitis virus
  • Mice
  • Mice, Inbred Strains
  • Spleen
  • T-Lymphocyte Subsets
  • T-Lymphocytes, Cytotoxic
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Identity

International Standard Serial Number (ISSN)

  • 0022-1007

Digital Object Identifier (DOI)

  • 10.1084/jem.174.1.203

PubMed ID

  • 1905339
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Additional Document Info

start page

  • 203

end page

  • 212

volume

  • 174

issue

  • 1

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