Selection of HIV Variants with Signature Genotypic Characteristics during Heterosexual Transmission

Abstract

Background Newly infected subjects acquire a limited number of human immunodeficiency virus type 1 (HIV-1) variants with specific genotypic and phenotypic features from the array of viruses present in a chronically infected transmitting partner. Methods We examined HIV-1 envelope sequences from the earliest available serum sample after HIV-1 acquisition in 13 newly infected subjects and from their epidemiologically linked HIV-1–infected heterosexual partner. Samples from both members were collected on the same day in the Rakai Community Cohort Study. Results Ten couples were infected with subtype D HIV-1, and 3 pairs had subtype A HIV-1. Newly infected subjects acquired a subset of the viruses that were circulating in the transmitting partner; transmitted variants had less diversity and divergence and were more closely related to the ancestral sequences. The majority of signature amino acid differences among donor and recipient sequences were in and immediately following the V3 loop. Envelopes from recipients were significantly shorter and had a lower V3 charge than envelopes from donors, but there was no significant difference in the number of potential N-linked glycosylation sites. Conclusion A minority subset of HIV-1 variants with signature genotypes is favored for transmission in this population.

Comparison of Viral Env Proteins from Acute and Chronic Infections with Subtype C Human Immunodeficiency Virus Type 1 Identifies Differences in Glycosylation and CCR5 Utilization and Suggests a New Strategy for Immunogen Design

“…In several studies, there has been consistent observation of reduced length of the variable regions in the Env protein and/or reduced N-linked glycosylation density of the Env protein, features reported for subtypes C, A, and D HIV-1 (4,19,20) but less clear for subtype B HIV-1 (19,21,22). An analysis of a large data set of subtype B env sequences revealed in the transmitted viruses selection for a basic amino acid at position 12 in the Env leader sequence that increases Env density on virions and underrepresentation of a glycosylation site at codon 413 (23,24), although this site is typically not present in subtype C HIV-1.…”

The Thai Phase III HIV Type 1 Vaccine Trial (RV144) Regimen Induces Antibodies That Target Conserved Regions Within the V2 Loop of gp120

“…62 Heterosexual transmission is usually a single infectious event and productive infection reflects the expansion of the founder virus. 36,63,64 The V2 loop has a number of features that might involve initial events in infection. It has a highly conserved length among early or transmitted/founder isolates and length and glycosylation of the V2 loop are commonly associated with escape from neutralizing antibodies.…”

Transmitted/Founder and Chronic HIV-1 Envelope Proteins Are Distinguished by Differential Utilization of CCR5

“…Several phenotypic characteristics are clearly associated with transmission: T/F Envs virtually always use CCR5 rather than CXCR4 or other noncanonical coreceptors (2,(16)(17)(18) and generally infect T cells but not macrophages (2,13,15,19) as a result of requiring relatively high levels of CD4 to mediate virus entry (20)(21)(22)(23)(24)(25). Other phenotypic and genotypic traits that have been linked to transmission are less well defined: Envs isolated from acute infection have sometimes been reported to be more neutralization sensitive (19), have on average fewer putative N-linked glycosylation sites (1,26), and have shorter variable loops (1,(27)(28)(29) compared to Envs isolated from chronically infected individuals.…”