Abstract
The V1 and V2 variable regions of the primate immunodeficiency viruses contribute to the trimer association domain of the gp120 exterior envelope glycoprotein. A pair of V2 cysteine residues at 183 and 191 (“twin cysteines”) is present in several simian immunodeficiency viruses, human immunodeficiency virus type 2 (HIV-2) and some SIVcpz lineages, but not in HIV-1. To examine the role of this potentially disulfide-bonded twin-cysteine motif, the cysteine residues in the SIVmac239 envelope glycoproteins were individually and pairwise substituted by alanine residues. All of the twin-cysteine mutants exhibited decreases in gp120 association with the Env trimer, membrane-fusing activity, and ability to support virus entry. Thus, the twin-cysteine motif plays a role in Env trimer stabilization in SIV and may do so in HIV-2 and some SIVcpz as well. This implies that HIV-1 lost the twin-cysteines, and may have relatively unstable Env trimers compared to SIV and HIV-2.
Highlights
It has been well established that human immunodeficiency viruses (HIV) are derived from simian immunodeficiency viruses (SIV) through cross-species transmission [1,2,3,4]
SIVcpz in chimpanzees, which represents the intermediate in primate lentiviruses (PLV) transmission from nonhuman primates to humans, can exhibit pathogenicity in chimpanzees resembling that of HIV-1 in humans [12,13,14,15]
We show that alteration of the twin-cysteine motif disrupts the stable and non-covalent association of SIVmac239 gp120 with the envelope glycoprotein (Env) trimer
Summary
It has been well established that human immunodeficiency viruses (HIV) are derived from simian immunodeficiency viruses (SIV) through cross-species transmission [1,2,3,4]. The basis for the differences between pathogenic HIV-1 infections in humans and the generally apathogenic SIV infections in African monkeys is not well understood. In the latter case, SIV and the host immune system apparently achieve a mutual balance. SIVcpz in chimpanzees, which represents the intermediate in PLV transmission from nonhuman primates to humans, can exhibit pathogenicity in chimpanzees resembling that of HIV-1 in humans [12,13,14,15]. SIV infection of monkeys, SIVcpz infection of chimpanzees, and HIV-1 infection of humans apparently represent examples of progressively poorer host immune system control of virus and increased pathogenicity
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