Phylogenetic and Phenotypic Analysis of HIV Type 1 Env gp120 in Cases of Subtype C Mother-to-Child Transmission

Abstract

Human immunodeficiency virus type 1 (HIV-1) subtype C constitutes a majority of the newly transmitted cases of HIV-1 in many developing countries. There is growing evidence suggesting that subtype C viruses may display characteristics that make them distinct from subtype B and other subtypes, and such differences may affect its transmission and pathogenesis in infected individuals. In this study, HIV-1 sequences from the C2-V4 region of the envelope gene were analyzed from four infected mother-infant pairs (MIPs) after perinatal transmission in Zambia. We found that all viral isolates from four Zambian MIPs were of the subtype C HIV-1 subgroup. All tested isolates were macrophage tropic and did not infect any tested T cell lines or form syncytia in vitro. In addition, the isolates appear to use exclusively the CCR5 coreceptor. Phylogenetic analyses clearly indicated two contrasting phylogenetic transmission patterns for the four MIPs analyzed in the present study. Three cases displayed a pattern of selective transmission of a single or a few variants, and one case was found to transmit multiple maternal HIV-1 variants to her infant. The differences in the mode and timing of transmission may account for the observed transmission pattern among four MIPs.

Neutralizing Antibody Escape during HIV-1 Mother-to-Child Transmission Involves Conformational Masking of Distal Epitopes in Envelope

“…MTCT studies were the first to illustrate the concept of an HIV-1 transmission bottleneck (76); despite a heterogeneous population in the chronically infected mother, only one variant is typically transmitted to the infant (1,29,58,63,69,77,82). These studies suggest that variants with certain properties may be selected during transmission, and similar findings have been obtained in cases of heterosexual transmission (59).…”

Coinfection with Schistosoma mansoni Reactivates Viremia in Rhesus Macaques with Chronic Simian-Human Immunodeficiency Virus Clade C Infection

“…R5 SHIV clade C. SHIV-1157ip (39) consists of an SHIV-vpu ϩ backbone (27) and encodes most of gp120 and all of the extracellular and transmembrane regions of gp41 of the primary HIV clade C strain HIV1157i, which had been isolated from a 6-month-old Zambian infant with in utero infection (43). The initial SHIV construct, the infectious molecular clone SHIV-1157i, was adapted by serial blood transfer through a cohort of five rhesus monkeys that consisted of two infants, two neonates, and one juvenile.…”

Structural Descriptors of gp120 V3 Loop for the Prediction of HIV-1 Coreceptor Usage

“…Indicator performs prediction based on an SVM using a binary sequence encoding, which uses a bit-vector to indicate the presence or absence of a specific amino acid at a specific V3 loop sequence position. We evaluated the two structural descriptors and the two sequence-based predictors on data compiled from the Los Alamos HIV Sequence Database and several publications [14,[34][35][36][37]. The evaluation is performed on a dataset containing 514 mutually distinct V3 sequences (SEQ indels,514 ) and a smaller subset, containing 432 sequences without indels (SEQ noindels,432 ).…”

“…From the HIV Sequence Database at Los Alamos National Laboratory and several publications [14,[34][35][36][37], we obtained 1,100 clonal samples with annotated coreceptor phenotype from 332 patients. To reduce the risk of positively biased results, we removed all duplicate V3 sequences (i.e., sequences with 100% sequence identity to another sequence in the dataset), resulting in 514 mutually distinct sequences.…”