Research Professor & Chief, Division of Research
Department of Obstetrics and Gynecology, University of Washington
Professor, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
Genetic and antiretroviral drug effects on immunity: from HIV prevention to chronic infection
Host:N. Chigorimbo Tsikiwa
Abstract
In Part I of my seminar, I show that nucleoside/nucleotide reverse transcriptase inhibitors, such as tenofovir, induce a chronic interferon-stimulated gene (ISG) signature across mucosal tissues, mediated in part by suppression of IL-10 via AKT/mTOR inhibition and by accumulation of RNA:DNA hybrids from blocked endogenous retroelement reverse transcription. Many of these same ISGs are upregulated during chronic HIV-1 infection, suggesting NRTIs may contribute to persistent immune activation and influence HIV latency dynamics. In Part II, if there is time, I present genetic evidence from African cohorts that CD101 immunoglobulin-like domain variants increase HIV-1 acquisition risk by upregulating AXL, a receptor that dampens antiviral type I interferon-JAK-STAT signaling.
Together, these studies show that antiretroviral drugs and host genetic variation both shape innate immunity, with implications for HIV acquisition and the subsequent course of infection.
International Seminar Programme
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