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 language | English (US) |
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Pages (from-to) | 74-88 |
Number of pages | 15 |
Journal | Virology |
Volume | 328 |
Issue number | 1 |
DOIs | |
State | Published - Oct 15 2004 |
Externally published | Yes |
Keywords
- Envelope
- HIV-1
- Homeostasis
- Intravenous
- Nef
- Pathogenesis
- Progression
- Replication
- Thymus
- Transmission
ASJC Scopus subject areas
- Virology