Selection for human immunodeficiency virus type 1 envelope glycosylation variants with shorter V1-V2 loop sequences occurs during transmission of certain genetic subtypes and may impact viral RNA levels.
Designing an effective human immunodeficiency virus type 1 (HIV-1) vaccine will rely on understanding which variants, from among the myriad of circulating HIV-1 strains, are most commonly transmitted and determining whether such variants have an Achilles heel. Here we show that heterosexually acquired subtype A HIV-1 envelopes have signature sequences that include shorter V1-V2 loop sequences and fewer predicted N-linked glycosylation sites relative to the overall population of circulating variants. In contrast, recently transmitted subtype B variants did not, and this was true for cases where the major risk factor was homosexual contact, as well as for cases where it was heterosexual contact. This suggests that selection during HIV-1 transmission may vary depending on the infecting subtype. There was evidence from 23 subtype A-infected women for whom there was longitudinal data that those who were infected with viruses with fewer potential N-linked glycosylation sites in V1-V2 had lower viral set point levels. Thus, our study also suggests that the extent of glycosylation in the infecting virus could impact disease progression.
Chohan
Bhavna
B
Division of Human Biology, Fred Hutchinson Cancer Center, 1100 Fairview Ave. N., C3-168 Seattle, WA 98109-1024, USA.
Lang
Dorothy
D
Sagar
Manish
M
Korber
Bette
B
Lavreys
Ludo
L
Richardson
Barbra
B
Overbaugh
Julie
J
D018450:Disease Progression; D018562:Disease Transmission, Infectious; D005260:Female; D014644:Genetic Variation; D006031:Glycosylation; D015699:HIV Envelope Protein gp120 / Q000235:genetics; D015658:HIV Infections / Q000175:diagnosis / Q000635:transmission / Q000821:virology*; D015497:HIV-1 / Q000235:genetics*; D020010:Heterosexuality; D006801:Humans; D007630:Kenya; D008297:Male; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000235:genetics; D014759:Viral Envelope Proteins / Q000235:genetics*; D019562:Viral Load
D015699:HIV Envelope Protein gp120; C059761:HIV envelope protein gp120 (135-148); D010446:Peptide Fragments; D014759:Viral Envelope Proteins