Primary Infection by a Human Immunodeficiency Virus with Atypical Coreceptor Tropism
Year: 2011
Type: article
Abstract: The great majority of human immunodeficiency virus type 1 (HIV-1) strains enter CD4+ target cells by interacting with one of two coreceptors, CCR5 or CXCR4. Here we describe a transmitted/founder (T/F) virus (ZP6248) that was profoundly impaired in its ability to utilize CCR5 and CXCR4 coreceptors on multiple CD4+ cell lines as well as primary human CD4+ T cells and macrophages in vitro yet replicated to very high titers (>80 million RNA copies/ml) in an acutely infected individual. Interestingly, the envelope (Env) glycoprotein of this clade B virus had a rare GPEK sequence in the crown of its third variable loop (V3) rather than the consensus GPGR sequence. Extensive sequencing of sequential plasma samples showed that the GPEK sequence was present in virtually all Envs, including those from the earliest time points after infection. The molecularly cloned (single) T/F virus was able to replicate, albeit poorly, in cells obtained from ccr5Δ32 homozygous donors. The ZP6248 T/F virus could also infect cell lines overexpressing the alternative coreceptors GPR15, APJ, and FPRL-1. A single mutation in the V3 crown sequence (GPEK->GPGK) of ZP6248 restored its infectivity in CCR5+ cells but reduced its ability to replicate in GPR15+ cells, indicating that the V3 crown motif played an important role in usage of this alternative coreceptor. These results suggest that the ZP6248 T/F virus established an acute in vivo infection by using coreceptor(s) other than CCR5 or CXCR4 or that the CCR5 coreceptor existed in an unusual conformation in this individual.
Source: Journal of Virology
DOI: 10.1128/jvi.05249-11
Authors: Chunlai Jiang, Nicholas F. Parrish, Craig B. Wilen, Hui Li, Yue Chen, Jeffrey W. Pavlicek, Anna Berg, Xiaozhi Lu, Hongshuo Song, John C. Tilton, Jennifer M. Pfaff, Elizabeth A. Henning, Julie M. Decker, M. Anthony Moody, Mark S. Drinker, Robert Schutte, Stephanie Freel, Georgia D. Tomaras, Rebecca Nedellec, Donald E. Mosier, Barton F. Haynes, George M. Shaw, Beatrice H. Hahn, Robert W. Doms, Feng Gao
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Awards: (CHAVI) Center for HIV/AIDS Vaccine Immunology, G1808123841, Medical Scientist Training Program, HIV entry and its inhibition, HIV Pathogenesis, Vaccination and Cure, (CHAVI) Center for HIV/AIDS Vaccine Immunology, Center for AIDS Research, Interdisciplinary Research Training Program in AIDS, UAB Center for AIDS Research (CFAR)
OpenAlex ID: W2005273976