CXCR4-tropic HIV-1 infection in an immunocompetent monkey model
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.
Authors
- Paul Gendler (ORCID: https://orcid.org/0000-0002-2113-4564)
- Nicholas R. Meyerson (ORCID: https://orcid.org/0000-0002-3238-8252)
- Sara L. Sawyer (ORCID: https://orcid.org/0000-0002-6965-1085)
- Obaiah Dirasantha
- Pyone P. Aye (ORCID: https://orcid.org/0000-0002-4764-3965)
- Bridget L. Burris
- Pramod N. Nehete (ORCID: https://orcid.org/0000-0002-2815-2677)
- Joseph L. Timpona
- George W. Tustin
- Sarah Kezar (ORCID: https://orcid.org/0000-0002-8423-0828)
- Gregory K. Wilkerson (ORCID: https://orcid.org/0000-0002-3773-1064)
- S. Scianna
- Vanessa L. Bauer (ORCID: https://orcid.org/0000-0003-0225-3215)
- Ryan T. Fahy
- Will T. Fattor
- Cody J. Warren (ORCID: https://orcid.org/0000-0003-4101-2705)
- Kathryn A. Shelton (ORCID: https://orcid.org/0000-0002-1754-1423)
- Arturo Barbachano-Guerrero (ORCID: https://orcid.org/0000-0001-7483-839X)
- Ron S. Veazey
- Jens Kuhn
- Emily R. Feldman
- Melisa J. Weiss
- Paul J. Koehle
- Adetunji S. Adesina
- C. Todd DeMarco
- Ava Fainberg
- Elizabeth I. Lindemann
- Sean E. Clark
- Analy Galvan
- Mackenzie L. Garnett
- Omar Davila
- Thomas N. Denny
- Maria D. Salinas
Institutions
- University of North Carolina at Chapel Hill (US)
- Tulane University (US)
- National Institutes of Health (US)
- University of North Carolina Health Care (US)
- The University of Texas MD Anderson Cancer Center (US)
- Duke University (US)
- University of Colorado Boulder (US)
- National Institute of Allergy and Infectious Diseases (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2026-03-09
- DOI
- https://doi.org/10.1038/s41467-026-70209-5
- Primary Topic
- HIV Research and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 0.00