Characterization of a thymus-tropic HIV-1 isolate from a rapid progressor: Role of the envelope

Eric G. Meissner, Karen M. Duus, Feng Gao, Xiao Fang Yu, Lishan Su

Research output: Contribution to journalArticlepeer-review

Abstract

Loss of T cell homeostasis usually precedes the onset of AIDS. We hypothesized that rapid progressors may be transmitted with HIV-1 that is particularly able to perturb T cell homeostasis. To this end, we have tested two transmitted, syncytium-inducing (SI) viral isolates from a rapid progressor in two thymus models. One of the isolates (R3A) exhibited markedly rapid kinetics of replication and thymocyte depletion. These phenotypes mapped to the envelope, as a recombinant NL4-3 virus encoding the R3A envelope had similar phenotypes, even in the absence of nef. Notably, the viruses with high pathogenic activity in the thymus (R3A and NL4-R3A) did not show enhanced replication or cytopathicity in PHA-stimulated PBMCs. Furthermore, NL4-R3A did not enhance replication of the coinfected NL4-3 virus in the thymus, suggesting an intrinsic advantage of the R3A envelope. The R3A envelope showed higher entry activity in infecting human T cells and in depleting CD4+ thymocytes when expressed in trans. These data suggest that SI viruses with unique envelope functions which can overcome barriers to transmission may hasten disease progression by perturbing T cell homeostasis.

Original languageEnglish (US)
Pages (from-to)74-88
Number of pages15
JournalVirology
Volume328
Issue number1
DOIs
StatePublished - Oct 15 2004

Keywords

  • Envelope
  • HIV-1
  • Homeostasis
  • Intravenous
  • Nef
  • Pathogenesis
  • Progression
  • Replication
  • Thymus
  • Transmission

ASJC Scopus subject areas

  • Virology

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