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The Impact of SIV-Induced Immunodeficiency on SARS-CoV-2 Disease, Viral Dynamics, and Antiviral Immune Response in a Nonhuman Primate Model of Coinfection
oleh: Alexandra Melton, Lori A. Rowe, Toni Penney, Clara Krzykwa, Kelly Goff, Sarah E. Scheuermann, Hunter J. Melton, Kelsey Williams, Nadia Golden, Kristyn Moore Green, Brandon Smith, Kasi Russell-Lodrigue, Jason P. Dufour, Lara A. Doyle-Meyers, Faith Schiro, Pyone P. Aye, Jeffery D. Lifson, Brandon J. Beddingfield, Robert V. Blair, Rudolf P. Bohm, Jay K. Kolls, Jay Rappaport, James A. Hoxie, Nicholas J. Maness
| Format: | Article |
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| Diterbitkan: | MDPI AG 2024-07-01 |
Deskripsi
The effects of immunodeficiency associated with chronic HIV infection on COVID-19 disease and viral persistence have not been directly addressed in a controlled setting. In this pilot study, we exposed two pigtail macaques (PTMs) chronically infected with SIVmac239, exhibiting from very low to no CD4 T cells across all compartments, to SARS-CoV-2. We monitored the disease progression, viral replication, and evolution, and compared these outcomes with SIV-naïve PTMs infected with SARS-CoV-2. No overt signs of COVID-19 disease were observed in either animal, and the SARS-CoV-2 viral kinetics and evolution in the SIVmac239 PTMs were indistinguishable from those in the SIV-naïve PTMs in all sampled mucosal sites. However, the single-cell RNA sequencing of bronchoalveolar lavage cells revealed an infiltration of functionally inert monocytes after SARS-CoV-2 infection. Critically, neither of the SIV-infected PTMs mounted detectable anti-SARS-CoV-2 T-cell responses nor anti-SARS-CoV-2 binding or neutralizing antibodies. Thus, HIV-induced immunodeficiency alone may not be sufficient to drive the emergence of novel viral variants but may remove the ability of infected individuals to mount adaptive immune responses against SARS-CoV-2.