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 journalArticle

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

Fingerprint

Thymus Gland
HIV-1
Viruses
T-Lymphocytes
Homeostasis
Giant Cells
Thymocytes
Phenotype
Disease Progression
Acquired Immunodeficiency Syndrome

Keywords

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

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

Cite this

Characterization of a thymus-tropic HIV-1 isolate from a rapid progressor : Role of the envelope. / Meissner, Eric G.; Duus, Karen M.; Gao, Feng; Yu, Xiao Fang; Su, Lishan.

In: Virology, Vol. 328, No. 1, 15.10.2004, p. 74-88.

Research output: Contribution to journalArticle

Meissner, Eric G. ; Duus, Karen M. ; Gao, Feng ; Yu, Xiao Fang ; Su, Lishan. / Characterization of a thymus-tropic HIV-1 isolate from a rapid progressor : Role of the envelope. In: Virology. 2004 ; Vol. 328, No. 1. pp. 74-88.
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