Conserved V3 loop sequences and transmission of human immunodeficiency virus type 1.
The third variable region (V3) of the surface glycoprotein (gp120) of envelope sequence subtype B, type 1 human immunodeficiency virus (HIV-1B), is highly variable among T cell line-adapted viruses and syncytium-inducing HIV-1-B isolates. Here we analyze the V3 region sequences from 93 individuals close to the time of seroconversion and show that the cysteine-bridged V3 loop, which also encompasses a major neutralizing determinant, is highly conserved, whereas sequences immediately surrounding the loop are similarly divergent in all HIV-1-B strains. Viruses with this conserved V3 loop have been reported to be more resistant to antibody-mediated neutralization than T cell-adapted viruses with divergent V3 sequences. We hypothesize, therefore, that on transmission from a donor to a recipient, virions inherently more resistant to neutralization by donor antibodies have a greater chance of initiating infection than those more sensitive to neutralization. This might explain the conservation of V3 early in infection and has implications for the design of HIV vaccines.
Shpaer
E G
EG
Department of Microbiology and Immunology, Stanford University School of Medicine, California 94305-5402.
Delwart
E L
EL
Kuiken
C L
CL
Goudsmit
J
J
Bachmann
M H
MH
Mullins
J I
JI
D000595:Amino Acid Sequence; D002460:Cell Line; D017124:Conserved Sequence; D018450:Disease Progression; D015699:HIV Envelope Protein gp120 / Q000235:genetics*; D015658:HIV Infections / Q000276:immunology / Q000635:transmission* / Q000821:virology*; D006679:HIV Seropositivity; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology / Q000472:pathogenicity; D006801:Humans; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D010446:Peptide Fragments / Q000235:genetics*; D011533:Proviruses / Q000235:genetics; D017386:Sequence Homology, Amino Acid
D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments