HIV efficiently infects T cells from the endometrium and remodels them to promote systemic viral spread
Tongcui Ma,
Xiaoyu Luo,
Ashley F George,
Gourab Mukherjee,
Nandini Sen,
Trimble L Spitzer,
Linda C Giudice,
Warner C Greene,
Nadia R Roan
Affiliations
Tongcui Ma
Gladstone Institute of Virology and Immunology, San Francisco, United States; Department of Urology, University of California, San Francisco, San Francisco, United States
Xiaoyu Luo
Gladstone Institute of Virology and Immunology, San Francisco, United States
Ashley F George
Gladstone Institute of Virology and Immunology, San Francisco, United States; Department of Urology, University of California, San Francisco, San Francisco, United States
Gourab Mukherjee
Department of Data Sciences and Operations, University of Southern California, Los Angeles, United States
Nandini Sen
Departments of Pediatrics and Microbiology and Immunology, Stanford School of Medicine, Stanford, United States
Trimble L Spitzer
Lt Col, United States AF; Women’s Health Clinic, Naval Medical Center, Portsmouth, United States
Linda C Giudice
Center for Reproductive Sciences, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, San Francisco, United States
Warner C Greene
Gladstone Institute of Virology and Immunology, San Francisco, United States; Department of Medicine, University of California, San Francisco, San Francisco, United States
Gladstone Institute of Virology and Immunology, San Francisco, United States; Department of Urology, University of California, San Francisco, San Francisco, United States
The female reproductive tract (FRT) is the most common site of infection during HIV transmission to women, but viral remodeling complicates characterization of cells targeted for infection. Here, we report extensive phenotypic analyses of HIV-infected endometrial cells by CyTOF, and use a ‘nearest neighbor’ bioinformatics approach to trace cells to their original pre-infection phenotypes. Like in blood, HIV preferentially targets memory CD4+ T cells in the endometrium, but these cells exhibit unique phenotypes and sustain much higher levels of infection. Genital cell remodeling by HIV includes downregulating TCR complex components and modulating chemokine receptor expression to promote dissemination of infected cells to lymphoid follicles. HIV also upregulates the anti-apoptotic protein BIRC5, which when blocked promotes death of infected endometrial cells. These results suggest that HIV remodels genital T cells to prolong viability and promote viral dissemination and that interfering with these processes might reduce the likelihood of systemic viral spread.
