SIV/SARS-CoV-2 coinfection in rhesus macaques impacts viral shedding, host immunity, the microbiome, and viral evolution
People living with HIV (PLWH) have an increased risk of severe COVID-19, including prolonged viral shedding and emergence of mutations. To investigate the simian immunodeficiency virus (SIV) macaque model for HIV/SARS-CoV-2 coinfection, seven SIV+ rhesus macaques were co-infected with SARS-CoV-2. COVID-19 in all macaques was mild. SARS-CoV-2 replication persisted in the upper, but not the lower respiratory tract for 14 days post-infection. Animals showed impaired generation of anti-SARS-CoV-2 antibodies and T-cells. Animals also displayed transient changes in microbial communities in the upper airway and gastrointestinal tract. Evidence of SARS-CoV-2 evolution was observed in the upper respiratory tract. This study demonstrates that SIV/SARS-CoV-2 coinfection in rhesus macaques recapitulates aspects of COVID-19 in PLWH. We show that SIV impairs anti-SARS-CoV-2 immunity, potentially leading to prolonged viral shedding, altered pathogenesis, and viral evolution. This highlights the importance of HIV status in COVID-19 and supports the use of this model for HIV/SARS-CoV-2 coinfection.
Authors
- Linhui Hao (ORCID: https://orcid.org/0000-0002-7325-1009)
- Dustin R. Long (ORCID: https://orcid.org/0000-0001-6365-953X)
- Cecily C. Midkiff (ORCID: https://orcid.org/0000-0001-9322-8730)
- Stephen J. Salipante (ORCID: https://orcid.org/0000-0001-8355-6992)
- Carter J. McCormick (ORCID: https://orcid.org/0009-0007-9341-2870)
- Paul T. Edlefsen (ORCID: https://orcid.org/0000-0002-8393-8103)
- Michael Gale (ORCID: https://orcid.org/0000-0002-6332-7436)
- Adam Waalkes (ORCID: https://orcid.org/0000-0002-5202-1108)
- Megan Fredericks (ORCID: https://orcid.org/0009-0002-8865-9688)
- Kaitlin Sawatzki (ORCID: https://orcid.org/0000-0002-7933-3064)
- Jane Barrow (ORCID: https://orcid.org/0000-0003-1899-9898)
- Robert V. Blair (ORCID: https://orcid.org/0000-0001-9616-9414)
- Alexander L. Greninger (ORCID: https://orcid.org/0000-0002-7443-0527)
- Megan A. O’Connor (ORCID: https://orcid.org/0000-0003-2127-5073)
- Simret Beraki
- DEBORAH HEYDENBURG FULLER (ORCID: https://orcid.org/0000-0001-7315-2441)
- Kelsi Penewit (ORCID: https://orcid.org/0000-0003-1454-6381)
- Zohar Kolodner
Institutions
- Oregon National Primate Research Center (US)
- Tulane University (US)
- University of Minnesota (US)
- University of Washington (US)
- Fred Hutch Cancer Center (US)
- Twin Cities Orthopedics (US)
Publication Details
- Journal
- Frontiers in Immunology
- Published
- 2025-05-20
- DOI
- https://doi.org/10.3389/fimmu.2025.1587688
- Citations
- 1
- Primary Topic
- HIV Research and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 1.04
Funders
- National Institutes of Health
- National Institute of Mental Health
- NIH Office of the Director