CXCR4-tropic HIV-1 infection in an immunocompetent monkey model

Nicholas R Meyerson; Vanessa L Bauer; Will T Fattor; Cody J Warren; Arturo Barbachano-Guerrero; Melisa J Weiss; Obaiah Dirasantha; Bridget L Burris; Adetunji S Adesina; Joseph L Timpona; Emily R Feldman; Ryan T Fahy; Paul Gendler; Ava Fainberg; Pramod N Nehete; Kathryn A Shelton; Analy Galvan; George W Tustin; Paul J Koehle; Maria D Salinas; Omar Davila; Elizabeth I Lindemann; Sean E Clark; Mackenzie L Garnett; C Todd DeMarco; Salvatore R Scianna; Thomas N Denny; Jens H Kuhn; Pyone P Aye; Ron S Veazey; Sarah M Kezar; Gregory K Wilkerson; Sara L Sawyer

doi:10.1038/s41467-026-70209-5

CXCR4-tropic HIV-1 infection in an immunocompetent monkey model

Nat Commun. 2026 Mar 9;17(1):3691. doi: 10.1038/s41467-026-70209-5.

Authors

Nicholas R Meyerson^#¹, Vanessa L Bauer^#¹, Will T Fattor^#¹, Cody J Warren¹, Arturo Barbachano-Guerrero¹, Melisa J Weiss², Obaiah Dirasantha¹, Bridget L Burris², Adetunji S Adesina¹, Joseph L Timpona¹, Emily R Feldman¹, Ryan T Fahy¹, Paul Gendler¹, Ava Fainberg¹, Pramod N Nehete², Kathryn A Shelton², Analy Galvan², George W Tustin², Paul J Koehle², Maria D Salinas², Omar Davila², Elizabeth I Lindemann², Sean E Clark², Mackenzie L Garnett², C Todd DeMarco³, Salvatore R Scianna³, Thomas N Denny³, Jens H Kuhn⁴, Pyone P Aye⁵, Ron S Veazey⁵, Sarah M Kezar², Gregory K Wilkerson^{6

7}, Sara L Sawyer⁸

Affiliations

¹ BioFrontiers Institute, Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO, 80303, USA.
² Department of Comparative Medicine, Michale E. Keeling Center for Comparative Medicine and Research, The University of Texas MD Anderson Cancer Center, Bastrop, TX, USA.
³ Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA.
⁴ Integrated Research Facility at Fort Detrick, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, MD, USA.
⁵ Tulane National Biomedical Research Center, 18703 Three Rivers Road, Covington, LA, USA.
⁶ Department of Comparative Medicine, Michale E. Keeling Center for Comparative Medicine and Research, The University of Texas MD Anderson Cancer Center, Bastrop, TX, USA. gwilker@email.unc.edu.
⁷ Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC, USA. gwilker@email.unc.edu.
⁸ BioFrontiers Institute, Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO, 80303, USA. ssawyer@colorado.edu.

^# Contributed equally.

Abstract

Current animal models of HIV-1 infection are either immunocompromised or rely on proxy viruses instead of HIV-1. Here, we establish an immunocompetent animal model for CXCR4-tropic HIV-1 in owl monkeys (Aotus nancymaae). Through analysis of 191 owl monkeys, genetic characterization and functional testing demonstrate that CD4 and Tetherin in this species support HIV-1 replication. Although owl monkeys do carry restrictive TRIMCyp and APOBEC3G alleles, small changes to the HIV-1 genome allow the virus to overcome these barriers. The resulting virus remains 93% wildtype HIV-1 in sequence. Fully immunocompetent owl monkeys can be infected with this virus, recapitulating key aspects of HIV-1 infection in humans: an initial surge of virus replication, subsequent establishment of a durable set point viremia, seroconversion, and the formation of a viral reservoir. The owl monkey model broadens the experimental options for HIV-1 research, and future studies will explore its utility for CCR5-tropic virus strains.

MeSH terms

Animals
Aotidae* / virology
CD4 Antigens / genetics
CD4 Antigens / metabolism
Disease Models, Animal
HIV Infections* / immunology
HIV Infections* / virology
HIV-1* / genetics
HIV-1* / physiology
Humans
Immunocompetence
Receptors, CXCR4* / metabolism
Viral Tropism
Virus Replication

Substances

Receptors, CXCR4
CD4 Antigens

Abstract

MeSH terms

Substances

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