1887

Abstract

Human immunodeficiency virus type 2 (HIV-2) infections cause severe immunodeficiency in humans, although HIV-2 is associated frequently with reduced virulence and pathogenicity compared to HIV-1. Genetic determinants that play a role in HIV pathogenesis are relatively poorly understood but has been implicated in inducing a more pathogenic phenotype . However, relatively little is known about the role of in HIV-2 pathogenesis. To address this, the genetic composition of 44 alleles from 37 HIV-2-infected individuals in Portugal, encompassing a wide spectrum of disease associations, CD4 counts and virus load, has been assessed. All alleles were subtype A, with no evidence of gross deletions, truncations or disruptions in the -encoding sequence; all were full-length and intact. HIV-2 long terminal repeat sequences were conserved and also indicated subtype A infections. Detailed analysis of motifs that mediate function in HIV-1 and simian immunodeficiency virus, such as CD4 downregulation and putative SH2/SH3 interactions, revealed significant natural variation. In particular, the central PxxPLR motif exhibited wide interpatient variation, ranging from an HIV-1-like tetra-proline structure (PxxP) to a disrupted minimal core motif (PxxQLR). The P→Q substitution was associated with an asymptomatic phenotype (Fisher's exact test, =0·026) and low virus loads. These data indicate that discrete differences in the gene sequence rather than gross structural changes are more likely to play a role in HIV-2 pathogenesis mediated via specific functional interactions.

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2003-05-01
2019-10-21
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