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Kinetics of Early Innate Immune Activation during HIV-1 Infection of Humanized Mice. Skelton, Jessica Katy Ortega-Prieto, Ana María Kaye, Steve Jimenez-Guardeño, Jose Manuel Turner, Jane Malim, Michael H. Towers, Greg J. Dorner, Marcus Virología - Investigación Virus del SIDA Modelos animales en investigación SIDA - Modelos animales Virology Virus HIV Human immunodeficiency virus type 1 (HIV-1) infection is associated with aberrant immune activation; however, most model systems for HIV-1 have been used during established infection. Here, we utilize ultrasensitive HIV-1 quantification to delineate early events during the eclipse, burst, and chronic phases of HIV-1 infection in humanized mice. We show that very early in infection, HIV-1 suppresses peripheral type I interferon (IFN) and interferon-stimulated gene (ISG) responses, including the HIV-1 restriction factor IFI44. At the peak of innate immune activation, prior to CD4 T cell loss, HIV-1 infection differentially affects peripheral and lymphoid Toll-like receptor (TLR) expression profiles in T cells and macrophages. This results in a trend toward an altered activation of nuclear factor κB (NF-κB), TANK-binding kinase 1 (TBK1), and interferon regulatory factor 3 (IRF3). The subsequent type I and III IFN responses result in preferential induction of peripheral ISG responses. Following this initial innate immune activation, peripheral expression of the HIV-1 restriction factor SAM domain- and HD domain-containing protein 1 (SAMHD1) returns to levels below those observed in uninfected mice, suggesting that HIV-1 interferes with their basal expression. However, peripheral cells still retain their responsiveness to exogenous type I IFN, whereas splenic cells show a reduction in select ISGs in response to IFN. This demonstrates the highly dynamic nature of very early HIV-1 infection and suggests that blocks to the induction of HIV-1 restriction factors contribute to the establishment of viral persistence 2024-12-02T10:33:42Z 2024-12-02T10:33:42Z 2019-05-15 journal article VoR Skelton JK, Ortega-Prieto AM, Kaye S, Jimenez-Guardeño JM, Turner J, Malim MH, Towers GJ, Dorner M.2019.Kinetics of Early Innate Immune Activation during HIV-1 Infection of Humanized Mice. J Virol93:10.1128/jvi.02123-18.https://doi.org/10.1128/jvi.02123-18 https://hdl.handle.net/10630/35418 10.1128/JVI.02123-18 eng Attribution-NonCommercial-NoDerivatives 4.0 Internacional http://creativecommons.org/licenses/by-nc-nd/4.0/ open access application/pdf ASM Journals