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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Meissner, EG; Duus, KM; Gao, F; Yu, X-F; Su, L

Published Date

  • October 10, 2004

Published In

Volume / Issue

  • 328 / 1

Start / End Page

  • 74 - 88

PubMed ID

  • 15380360

Pubmed Central ID

  • 15380360

International Standard Serial Number (ISSN)

  • 0042-6822

Digital Object Identifier (DOI)

  • 10.1016/j.virol.2004.07.019

Language

  • eng

Conference Location

  • United States