Format

Send to

Choose Destination
Cell. 2006 Jun 16;125(6):1055-67.

Nef-mediated suppression of T cell activation was lost in a lentiviral lineage that gave rise to HIV-1.

Author information

1
Department of Virology, University of Ulm, 89081 Ulm, Germany.

Abstract

High-level immune activation and T cell apoptosis represent a hallmark of HIV-1 infection that is absent from nonpathogenic SIV infections in natural primate hosts. The mechanisms causing these varying levels of immune activation are not understood. Here, we report that nef alleles from the great majority of primate lentiviruses, including HIV-2, downmodulate TCR-CD3 from infected T cells, thereby blocking their responsiveness to activation. In contrast, nef alleles from HIV-1 and a subset of closely related SIVs fail to downregulate TCR-CD3 and to inhibit cell death. Thus, Nef-mediated suppression of T cell activation is a fundamental property of primate lentiviruses that likely evolved to maintain viral persistence in the context of an intact host immune system. This function was lost during viral evolution in a lineage that gave rise to HIV-1 and may have predisposed the simian precursor of HIV-1 for greater pathogenicity in humans.

PMID:
16777597
DOI:
10.1016/j.cell.2006.04.033
[Indexed for MEDLINE]
Free full text

Publication types, MeSH terms, Substances, Secondary source ID, Grant support

Publication types

MeSH terms

Substances

Secondary source ID

Grant support

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center