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ResearchIn-Press PreviewAIDS/HIVImmunology Open Access | 10.1172/jci.insight.198743

RhCMV Expands CCR5 Memory T Cells and promotes SIV reservoir seeding in the Gut Mucosa

Chrysostomos Perdios,1 Naveen Suresh Babu,1 Celeste D. Coleman,1 Anna T. Brown,1 Shevon N. Alexander,1 Matilda J. Moström,1 Carolina Allers,1 Lara Doyle-Meyers,2 Christine M. Fennessey,3 Lori A. Rowe,4 Brandon F. Keele,3 Amitinder Kaur,1 Michael L. Freeman,5 and Joseph C. Mudd1

1Division of Immunology, Tulane National Primate Research Center, Covington, United States of America

2Division of Veterinary Medicine, Tulane National Primate Research Center, Covington, United States of America

3AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, United States of America

4Division of Microbiology, Tulane National Primate Research Center, Covington, United States of America

5Division of Infectious Diseases & HIV Medicine, Case Western Reserve University, Cleveland, United States of America

Find articles by Perdios, C. in: PubMed | Google Scholar

1Division of Immunology, Tulane National Primate Research Center, Covington, United States of America

2Division of Veterinary Medicine, Tulane National Primate Research Center, Covington, United States of America

3AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, United States of America

4Division of Microbiology, Tulane National Primate Research Center, Covington, United States of America

5Division of Infectious Diseases & HIV Medicine, Case Western Reserve University, Cleveland, United States of America

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1Division of Immunology, Tulane National Primate Research Center, Covington, United States of America

2Division of Veterinary Medicine, Tulane National Primate Research Center, Covington, United States of America

3AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, United States of America

4Division of Microbiology, Tulane National Primate Research Center, Covington, United States of America

5Division of Infectious Diseases & HIV Medicine, Case Western Reserve University, Cleveland, United States of America

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1Division of Immunology, Tulane National Primate Research Center, Covington, United States of America

2Division of Veterinary Medicine, Tulane National Primate Research Center, Covington, United States of America

3AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, United States of America

4Division of Microbiology, Tulane National Primate Research Center, Covington, United States of America

5Division of Infectious Diseases & HIV Medicine, Case Western Reserve University, Cleveland, United States of America

Find articles by Brown, A. in: PubMed | Google Scholar

1Division of Immunology, Tulane National Primate Research Center, Covington, United States of America

2Division of Veterinary Medicine, Tulane National Primate Research Center, Covington, United States of America

3AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, United States of America

4Division of Microbiology, Tulane National Primate Research Center, Covington, United States of America

5Division of Infectious Diseases & HIV Medicine, Case Western Reserve University, Cleveland, United States of America

Find articles by Alexander, S. in: PubMed | Google Scholar

1Division of Immunology, Tulane National Primate Research Center, Covington, United States of America

2Division of Veterinary Medicine, Tulane National Primate Research Center, Covington, United States of America

3AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, United States of America

4Division of Microbiology, Tulane National Primate Research Center, Covington, United States of America

5Division of Infectious Diseases & HIV Medicine, Case Western Reserve University, Cleveland, United States of America

Find articles by Moström, M. in: PubMed | Google Scholar |

1Division of Immunology, Tulane National Primate Research Center, Covington, United States of America

2Division of Veterinary Medicine, Tulane National Primate Research Center, Covington, United States of America

3AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, United States of America

4Division of Microbiology, Tulane National Primate Research Center, Covington, United States of America

5Division of Infectious Diseases & HIV Medicine, Case Western Reserve University, Cleveland, United States of America

Find articles by Allers, C. in: PubMed | Google Scholar

1Division of Immunology, Tulane National Primate Research Center, Covington, United States of America

2Division of Veterinary Medicine, Tulane National Primate Research Center, Covington, United States of America

3AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, United States of America

4Division of Microbiology, Tulane National Primate Research Center, Covington, United States of America

5Division of Infectious Diseases & HIV Medicine, Case Western Reserve University, Cleveland, United States of America

Find articles by Doyle-Meyers, L. in: PubMed | Google Scholar |

1Division of Immunology, Tulane National Primate Research Center, Covington, United States of America

2Division of Veterinary Medicine, Tulane National Primate Research Center, Covington, United States of America

3AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, United States of America

4Division of Microbiology, Tulane National Primate Research Center, Covington, United States of America

5Division of Infectious Diseases & HIV Medicine, Case Western Reserve University, Cleveland, United States of America

Find articles by Fennessey, C. in: PubMed | Google Scholar |

1Division of Immunology, Tulane National Primate Research Center, Covington, United States of America

2Division of Veterinary Medicine, Tulane National Primate Research Center, Covington, United States of America

3AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, United States of America

4Division of Microbiology, Tulane National Primate Research Center, Covington, United States of America

5Division of Infectious Diseases & HIV Medicine, Case Western Reserve University, Cleveland, United States of America

Find articles by Rowe, L. in: PubMed | Google Scholar

1Division of Immunology, Tulane National Primate Research Center, Covington, United States of America

2Division of Veterinary Medicine, Tulane National Primate Research Center, Covington, United States of America

3AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, United States of America

4Division of Microbiology, Tulane National Primate Research Center, Covington, United States of America

5Division of Infectious Diseases & HIV Medicine, Case Western Reserve University, Cleveland, United States of America

Find articles by Keele, B. in: PubMed | Google Scholar |

1Division of Immunology, Tulane National Primate Research Center, Covington, United States of America

2Division of Veterinary Medicine, Tulane National Primate Research Center, Covington, United States of America

3AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, United States of America

4Division of Microbiology, Tulane National Primate Research Center, Covington, United States of America

5Division of Infectious Diseases & HIV Medicine, Case Western Reserve University, Cleveland, United States of America

Find articles by Kaur, A. in: PubMed | Google Scholar |

1Division of Immunology, Tulane National Primate Research Center, Covington, United States of America

2Division of Veterinary Medicine, Tulane National Primate Research Center, Covington, United States of America

3AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, United States of America

4Division of Microbiology, Tulane National Primate Research Center, Covington, United States of America

5Division of Infectious Diseases & HIV Medicine, Case Western Reserve University, Cleveland, United States of America

Find articles by Freeman, M. in: PubMed | Google Scholar |

1Division of Immunology, Tulane National Primate Research Center, Covington, United States of America

2Division of Veterinary Medicine, Tulane National Primate Research Center, Covington, United States of America

3AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, United States of America

4Division of Microbiology, Tulane National Primate Research Center, Covington, United States of America

5Division of Infectious Diseases & HIV Medicine, Case Western Reserve University, Cleveland, United States of America

Find articles by Mudd, J. in: PubMed | Google Scholar

Published November 25, 2025 - More info

JCI Insight. https://doi.org/10.1172/jci.insight.198743.
Copyright © 2025, Perdios et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published November 25, 2025 - Version history
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Abstract

Cytomegalovirus (CMV) is a prevalent β-herpesvirus that persists asymptomatically in immunocompetent hosts. In people with HIV-1 (PWH), CMV is associated with HIV-1 persistence and particular inflammatory-related co-morbidities. The true causative role of CMV in HIV-associated pathologies however remains unclear given that nearly all PWH are coinfected with CMV. In this study, we examined acute phase immune and virological dynamics in cohorts of SIV-infected rhesus macaques (RMs) that were naturally seropositive or -negative for rhesus CMV (RhCMV). We observed prior to SIV, RhCMV expanded a polyclonal population of target CCR5+CD4+ T cells in gut and lymph nodes (LN) that expressed the chemotactic receptor CXCR3 and were largely not specific for RhCMV. Upon SIV infection, RhCMV+ RMs exhibited higher peak viremia and elevated levels of SIV DNA in the upper and lower intestine. Greater seeding of SIV DNA was associated with a maintenance of CCR5-expressing CD4+ T cells that were enriched within the RhCMV+ gut along a CXCR3-CXCL9 chemotactic axis. Overall, the data suggest that RhCMV can promote SIV susceptibility within a diverse, polyclonal pool of CD4 T cells that are not entirely RhCMV-specific.

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