Genetic Characteristics of HIV-1 Env in the Genital Tract of African Heterosexual Transmission Pairs

Publication Type:

Journal Article

Source:

AIDS Research and Human Retroviruses, Volume 29, Number 11, p.A76-A77 (2013)

ISBN:

0889-2229

Keywords:

2013, December 2013, Immunology, Infectious Diseases, Vaccine and Infectious Disease Division, Virology

Abstract:

Background: A better understanding of characteristics that define mucosally-transmitted HIV-1 may inform vaccine design. Commonly, a single CCR5-tropic virus establishes infection. In cross-sectional studies, histidine in Env leader peptide position 12 (His-12) is more frequent in blood-derived subtype B viruses from early compared to chronic infection, but few data exist for nonclade B or genital tract-derived viruses. Methods: Full-length HIV-1 env was sequenced from multiple viral templates in seminal plasma and endocervical swabs from 9 African male-to-female transmission pairs in the Partners in Prevention HSV/HIV Transmission Study. Viral genetic diversity, chemokine co-receptor usage, and Env position 12 residues were evaluated. Results: A mean of 14 sequences (SD= 6) was obtained from each participant. Couples were infected withHIV-1 subtypesAorA1/C (N = 4), C (N = 3), and D (N= 2). Seroconverters had less variable sequences compared to transmitters (pairwise genetic distance 0.5% versus 1.4%, Student’s t-test p = 0.007). Within transmission pairs, mean pairwise distance between the most closely related sequences was 1.3% (SD= 0.7%). Viruses were predicted to be CCR5-tropic, except in one transmitter with 7/16 CXCR4-tropic viruses. At Env position 12, 17 participants had homogenous viral templates, encoding glutamine (N= 8), asparagine (N= 3), histidine (N = 4), and arginine (N = 2). Partners in these transmitting couples shared Env position 12, with the exception of one couple with asparagine in 15/15 seroconverter and 17/19 transmitter sequences, and aspartate in 2/19 transmitter sequences. Conclusion: Genital tract viruses within African male-to-female HIV-1 transmission pairs show evidence of a genetic bottleneck and predominant CCR5 co-receptor usage. In this small study, multiple variants were rarely observed at Env position 12 in transmitters and His-12 was not found with increased frequency in seroconverters. Further studies are underway to determine the significance of Env position 12 in transmission of non-clade B viruses.

Notes:

PT: J; CT: Conference on AIDS Vaccine; CY: OCT 07-10, 2013; CL: Barcelona, SPAIN; NR: 0; TC: 0; J9: AIDS RES HUM RETROV; SI: SI; PG: 2; GA: 239PI