Journal article
SAMHD1 Promotes the Antiretroviral Adaptive Immune Response in Mice Exposed to Lipopolysaccharide
The Journal of immunology (1950), Vol.208(2), pp.444-453
01/15/2022
DOI: 10.4049/JIMMUNOL.2001389
PMCID: PMC8755609
PMID: 34893529
Abstract
SAMHD1 is a potent HIV-1 restriction factor that blocks reverse transcription in monocytes, dendritic cells and resting CD4
T cells by decreasing intracellular dNTP pools. However, SAMHD1 may diminish innate immune sensing and Ag presentation, resulting in a weaker adaptive immune response. To date, the role of SAMHD1 on antiretroviral immunity remains unclear, as mouse SAMHD1 had no impact on murine retrovirus replication in prior in vivo studies. Here, we show that SAMHD1 significantly inhibits acute Friend retrovirus infection in mice. Pretreatment with LPS, a significant driver of inflammation during HIV-1 infection, further unmasked a role for SAMHD1 in influencing immune responses. LPS treatment in vivo doubled the intracellular dNTP levels in immune compartments of SAMHD1 knockout but not wild-type mice. SAMHD1 knockout mice exhibited higher plasma infectious viremia and proviral DNA loads than wild-type mice at 7 d postinfection (dpi), and proviral loads inversely correlated with a stronger CD8
T cell response. SAMHD1 deficiency was also associated with weaker NK, CD4
T and CD8
T cell responses by 14 dpi and weaker neutralizing Ab responses by 28 dpi. Intriguingly, SAMHD1 influenced these cell-mediated immune (14 dpi) and neutralizing Ab (28 dpi) responses in male but not female mice. Our findings formally demonstrate SAMHD1 as an antiretroviral factor in vivo that could promote adaptive immune responses in a sex-dependent manner. The requirement for LPS to unravel the SAMHD1 immunological phenotype suggests that comorbidities associated with a "leaky" gut barrier may influence the antiviral function of SAMHD1 in vivo.
Details
- Title: Subtitle
- SAMHD1 Promotes the Antiretroviral Adaptive Immune Response in Mice Exposed to Lipopolysaccharide
- Creators
- BradleyS Barrett - University of Colorado DenverDavid H Nguyen - University of Colorado DenverJoella Xu - Emory UniversityKejun Guo - University of Colorado DenverShravida Shetty - University of Colorado DenverSean T Jones - University of Colorado DenverKaylee L Mickens - University of Colorado DenverCaitlin Shepard - Emory UniversityAxel Roers - Technische Universität DresdenRayk Behrendt - Technische Universität DresdenLi Wu - Roy J. and Lucille A. Carver College of MedicineBaek Kim - Emory UniversityMario L Santiago - University of Colorado Denver
- Resource Type
- Journal article
- Publication Details
- The Journal of immunology (1950), Vol.208(2), pp.444-453
- DOI
- 10.4049/JIMMUNOL.2001389
- PMID
- 34893529
- PMCID
- PMC8755609
- NLM abbreviation
- J Immunol
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Grant note
- T32 AI007405 / NIAID NIH HHS R01 AI136581 / NIAID NIH HHS R01 AI116603 / NIAID NIH HHS R01 AI162633 / NIAID NIH HHS R01 AI141495 / NIAID NIH HHS R01 AI134220 / NIAID NIH HHS
- Language
- English
- Date published
- 01/15/2022
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984297424102771
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