The Impact of SIV-Induced Immunodeficiency on SARS-CoV-2 Disease, Viral Dynamics, and Antiviral Immune Response in a Nonhuman Primate Model of Coinfection
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
Affiliations
Alexandra Melton
Tulane National Primate Research Center, Covington, LA 70433, USA
Lori A. Rowe
Tulane National Primate Research Center, Covington, LA 70433, USA
Toni Penney
Tulane National Primate Research Center, Covington, LA 70433, USA
Clara Krzykwa
Tulane National Primate Research Center, Covington, LA 70433, USA
Kelly Goff
Tulane National Primate Research Center, Covington, LA 70433, USA
Sarah E. Scheuermann
Tulane National Primate Research Center, Covington, LA 70433, USA
Hunter J. Melton
Department of Statistics, Florida State University, Tallahassee, FL 32306, USA
Kelsey Williams
Tulane National Primate Research Center, Covington, LA 70433, USA
Nadia Golden
Tulane National Primate Research Center, Covington, LA 70433, USA
Kristyn Moore Green
Tulane National Primate Research Center, Covington, LA 70433, USA
Brandon Smith
Tulane National Primate Research Center, Covington, LA 70433, USA
Kasi Russell-Lodrigue
Tulane National Primate Research Center, Covington, LA 70433, USA
Jason P. Dufour
Tulane National Primate Research Center, Covington, LA 70433, USA
Lara A. Doyle-Meyers
Tulane National Primate Research Center, Covington, LA 70433, USA
Faith Schiro
Tulane National Primate Research Center, Covington, LA 70433, USA
Pyone P. Aye
Tulane National Primate Research Center, Covington, LA 70433, USA
Jeffery D. Lifson
AIDS and Cancer Viruses Program, Frederick National Laboratory, Frederick, MD 21701, USA
Brandon J. Beddingfield
Tulane National Primate Research Center, Covington, LA 70433, USA
Robert V. Blair
Tulane National Primate Research Center, Covington, LA 70433, USA
Rudolf P. Bohm
Tulane National Primate Research Center, Covington, LA 70433, USA
Jay K. Kolls
Departments of Medicine and Pediatrics, Center for Translational Research in Infection and Inflammation, Tulane University School of Medicine, New Orleans, LA 70112, USA
Jay Rappaport
Tulane National Primate Research Center, Covington, LA 70433, USA
James A. Hoxie
Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
Nicholas J. Maness
Tulane National Primate Research Center, Covington, LA 70433, USA
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.
