Female Genital Tract Shedding of CXCR4-Tropic HIV Type 1 Is Associated with a Majority Population of CXCR4-Tropic HIV Type 1 in Blood and Declining CD4(+) Cell Counts

• Type of Material: Article
• Authors: Richard E. Haaland, Centers for Disease Control and Prevention; Sharon T. Sullivan, Centers for Disease Control and Prevention; Tammy Evans-Strickfaden, Centers for Disease Control and Prevention; Jeffrey Lennox, Emory University; Clyde E. Hart, Centers for Disease Control and Prevention
• Language: English
• Date: 2012-11-05
• Publisher: Mary Ann Liebert
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © Copyright 2012, Mary Ann Liebert, Inc.
• Final Published Version (URL): http://dx.doi.org/10.1089/aid.2012.0004
• Title of Journal or Parent Work: AIDS Research and Human Retroviruses
• ISSN: 0889-2229
• Volume: 28
• Issue: 11
• Start Page: 1524
• End Page: 1532
• Keywords: Science & Technology; ANTIRETROVIRAL THERAPY; SEQUENCE VARIATION; V3 LOOP; IMMUNE-RESPONSES; VIROLOGY; Virology; IMMUNODEFICIENCY-VIRUS TYPE-1; TREATMENT INTERRUPTION; CORECEPTOR USAGE; VAGINAL SECRETIONS; Life Sciences & Biomedicine; IMMUNOLOGY; INFECTIOUS DISEASES; Immunology; SEXUAL TRANSMISSION; Infectious Diseases; NEUTRALIZING ANTIBODIES
• Research Categories: Health Sciences, Medicine and Surgery

Abstract

This study compared HIV-1 genotypes shed over time (≤3.5 years) in the vaginal secretions (VS) and blood plasma (BP) of 15 chronically infected women. Analysis of predicted coreceptor tropism (CCR5=R5, CXCR4=X4) for quasispecies shedding revealed three patterns: (1) viral quasispecies shed in both VS and BP were restricted to R5-tropism at all time points, (2) quasispecies shed in VS were restricted to R5-tropism at all time points but X4 quasispecies were identified in the BP at one or more time points, and (3) quasispecies shed in matched VS and BP both contained X4-tropic viruses. Overall, the frequency of X4 quasispecies circulation in VS was 2-fold less than in BP and detection of X4 virus in VS was more likely to occur when X4 quasispecies comprised more than 50% of BP viruses (p=0.01) and when declines in blood CD4 + lymphocyte levels were the greatest (p=0.038). Additionally, the mean number of predicted N-glycosylation sites between matched VS and BP samples was strongly correlated (r=0.86, p < 0.0001) with glycosylation densities in the following order (VS R5=BP R5 > BP X4 > VS X4). The X4 glycosylation densities may result from compartmentalization pressures in the female genital tract or the delayed appearance of these viruses in VS. Our results suggest that the presence of X4 virus in VS is associated with a threshold population of X4 quasispecies in BP, which are increasing during the HIV-induced failure of the human immune system.