Livia Kucman, Western University

Livia G. Kucman1, Mitchell J. Mumby1, Art FY. Poon1,2, Steve J. Reynolds3,4,5, Ronald M. Galiwango5, Jessica L. Prodger1,, Andrew D. Redd3,4,6, Jimmy D. Dikeakos1 ||| 1. Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University, London, ON Canada, 2.Department of Pathology and Laboratory Medicine, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada, 3.Laboratory of Immunoregulation, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Baltimore, Maryland, USA, 4.Department of Medicine, Johns Hopkins University, Baltimore, MA, USA, 5.Rakai Health Sciences Program, Kalisizo, Uganda, 6.Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa

Fighting & Responding

Human Immunodeficiency Virus Type 1 (HIV-1) persists in people living with HIV-1 (PLWH) on antiretroviral treatment (ART) due to a latently infected immune cell population termed the latent reservoir. Most latent reservoir research focuses on subtype B HIV-1, with limited studies on the non-subtype B strains prevalent in lower-income countries. We previously characterized the Major Histocompatibility Complex Class I (MHC-I) and CD4 downregulation ability of non-Subtype B Nef proteins from ART-supressed PLWH in Uganda and found a correlation between the decay rate of the latent reservoir and Nef-mediated MHC-I downregulation, but not CD4 downregulation. However, it remains unknown if other Nef functions can affect latent reservoir dynamics in PLWH. Of interest is SERINC5, a host restriction factor that reduces progeny virion infectivity and is also antagonized by Nef. Given SERINC5s role in viral infectivity, we hypothesized that the ability of non-Subtype B Nefs from PLWH in Uganda to downregulate SERINC5 would not correlate with latent reservoir decay rate, as de novo infections are not believed to occur in ART-supressed individuals. We evaluated 49 primary Nef isolates using an infection-based assay and quantified SERINC5 downregulation by flow cytometry, where we observed functional variability between isolates and individuals. As expected, this activity did not correlate with the rate of latent reservoir decay. However, we identified a significant inverse correlation between Nef-mediated MHC-I and SERINC5 downregulation (p=0.001). Overall, we aim to characterize non-subtype B Nef's ability to downregulate SERINC5, and its implications on the latent reservoir in those living with HIV-1.