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ResearchIn-Press PreviewAIDS/HIVInfectious disease
Open Access | 10.1172/JCI187992
1US Military HIV Research Program, Center for Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, United States of America
2Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America
3Viral Diseases Program, Center for Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, United States of America
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1US Military HIV Research Program, Center for Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, United States of America
2Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America
3Viral Diseases Program, Center for Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, United States of America
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1US Military HIV Research Program, Center for Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, United States of America
2Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America
3Viral Diseases Program, Center for Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, United States of America
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1US Military HIV Research Program, Center for Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, United States of America
2Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America
3Viral Diseases Program, Center for Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, United States of America
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1US Military HIV Research Program, Center for Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, United States of America
2Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America
3Viral Diseases Program, Center for Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, United States of America
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1US Military HIV Research Program, Center for Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, United States of America
2Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America
3Viral Diseases Program, Center for Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, United States of America
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1US Military HIV Research Program, Center for Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, United States of America
2Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America
3Viral Diseases Program, Center for Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, United States of America
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1US Military HIV Research Program, Center for Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, United States of America
2Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America
3Viral Diseases Program, Center for Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, United States of America
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1US Military HIV Research Program, Center for Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, United States of America
2Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America
3Viral Diseases Program, Center for Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, United States of America
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1US Military HIV Research Program, Center for Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, United States of America
2Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America
3Viral Diseases Program, Center for Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, United States of America
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1US Military HIV Research Program, Center for Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, United States of America
2Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America
3Viral Diseases Program, Center for Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, United States of America
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1US Military HIV Research Program, Center for Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, United States of America
2Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America
3Viral Diseases Program, Center for Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, United States of America
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1US Military HIV Research Program, Center for Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, United States of America
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3Viral Diseases Program, Center for Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, United States of America
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1US Military HIV Research Program, Center for Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, United States of America
2Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America
3Viral Diseases Program, Center for Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, United States of America
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2Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America
3Viral Diseases Program, Center for Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, United States of America
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1US Military HIV Research Program, Center for Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, United States of America
2Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America
3Viral Diseases Program, Center for Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, United States of America
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3Viral Diseases Program, Center for Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, United States of America
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2Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America
3Viral Diseases Program, Center for Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, United States of America
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3Viral Diseases Program, Center for Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, United States of America
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3Viral Diseases Program, Center for Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, United States of America
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Published May 8, 2025 - More info
We leveraged specimens from the RV217 prospective study that enrolled participants at high risk of HIV-1 acquisition to investigate how NK, conventional T cells, and unconventional T cells influence HIV-1 acquisition. We observed low levels of α4β7 expression on memory CD4 T cells and iNKT cells, two cell types highly susceptible to HIV-1 infection, in highly exposed seronegative (HESN) compared to highly exposed seroconverter (HESC) participants. NK cells from HESN had higher levels of α4β7 compared to HESC, presented a quiescent phenotype, and had a higher capacity to respond to opsonized target cells. We also measured translocated microbial products in plasma and found differences in phylum distribution between HESN and HESC that were associated with the immune phenotypes impacting the risk of HIV-1 acquisition. Finally, a logistic regression model combining features of NK cells activation, α4β7 expression on memory CD4 T cells, and Tbet expression by iNKT cells achieved the highest accuracy in identifying HESN and HESC participants. This immune signature comprised of increased α4β7 on cells susceptible to HIV infection combined with higher NK cells activation and lower gut homing potential could impact the efficacy of HIV-1 prevention strategies such as vaccines.