The Impact of SIV-Induced Immunodeficiency on Clinical Manifestation, Immune Response, and Viral Dynamics in SARS-CoV-2 Coinfection.

Autor: Melton A; Tulane National Primate Research Center, Covington, Louisiana.; Biomedical Science Training Program, Tulane University School of Medicine, New Orleans, Louisiana., Rowe LA; Tulane National Primate Research Center, Covington, Louisiana., Penney T; Tulane National Primate Research Center, Covington, Louisiana., Krzykwa C; Tulane National Primate Research Center, Covington, Louisiana., Goff K; Tulane National Primate Research Center, Covington, Louisiana., Scheuermann S; Tulane National Primate Research Center, Covington, Louisiana., Melton HJ; Florida State University, Department of Statistics, Tallahassee, Florida., Williams K; Tulane National Primate Research Center, Covington, Louisiana., Golden N; Tulane National Primate Research Center, Covington, Louisiana., Green KM; Tulane National Primate Research Center, Covington, Louisiana., Smith B; Tulane National Primate Research Center, Covington, Louisiana., Russell-Lodrigue K; Tulane National Primate Research Center, Covington, Louisiana.; Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana., Dufour JP; Tulane National Primate Research Center, Covington, Louisiana.; Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana., Doyle-Meyers LA; Tulane National Primate Research Center, Covington, Louisiana.; Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana., Schiro F; Tulane National Primate Research Center, Covington, Louisiana., Aye PP; Tulane National Primate Research Center, Covington, Louisiana.; Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana., Lifson JD; AIDS and Cancer Viruses Program, Frederick National Laboratory, Frederick, Maryland, United States of America., Beddingfield BJ; Tulane National Primate Research Center, Covington, Louisiana.; Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, Louisiana., Blair RV; Tulane National Primate Research Center, Covington, Louisiana., Bohm RP; Tulane National Primate Research Center, Covington, Louisiana.; Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana.; Present address: Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, Oregon., Kolls JK; Departments of Medicine and Pediatrics, Center for Translational Research in Infection and Inflammation, Tulane University School of Medicine, New Orleans, LA 70112, USA.; Department of Pulmonary Critical Care and Environmental Medicine, Tulane University School of Medicine, New Orleans, LA 70112, USA., Rappaport J; Tulane National Primate Research Center, Covington, Louisiana.; Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, Louisiana., Hoxie JA; Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania., Maness NJ; Tulane National Primate Research Center, Covington, Louisiana.; Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, Louisiana.
Jazyk: angličtina
Zdroj: BioRxiv : the preprint server for biology [bioRxiv] 2023 Nov 16. Date of Electronic Publication: 2023 Nov 16.
DOI: 10.1101/2023.11.15.567132
Abstrakt: Persistent and uncontrolled SARS-CoV-2 replication in immunocompromised individuals has been observed and may be a contributing source of novel viral variants that continue to drive the pandemic. Importantly, 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. Here we conducted a pilot study wherein two pigtail macaques (PTM) chronically infected with SIVmac239 were exposed to SARS-CoV-2 and monitored for six weeks for clinical disease, viral replication, and viral evolution, and compared to our previously published cohort of SIV-naïve PTM infected with SARS-CoV-2. At the time of SARS-CoV-2 infection, one PTM had minimal to no detectable CD4+ T cells in gut, blood, or bronchoalveolar lavage (BAL), while the other PTM harbored a small population of CD4+ T cells in all compartments. Clinical signs were not observed in either PTM; however, the more immunocompromised PTM exhibited a progressive increase in pulmonary infiltrating monocytes throughout SARS-CoV-2 infection. Single-cell RNA sequencing (scRNAseq) of the infiltrating monocytes revealed a less activated/inert phenotype. Neither SIV-infected PTM mounted detectable anti-SARS-CoV-2 T cell responses in blood or BAL, nor anti-SARS-CoV-2 neutralizing antibodies. Interestingly, despite the diminished cellular and humoral immune responses, SARS-CoV-2 viral kinetics and evolution were indistinguishable from SIV-naïve PTM in all sampled mucosal sites (nasal, oral, and rectal), with clearance of virus by 3-4 weeks post infection. SIV-induced immunodeficiency significantly impacted immune responses to SARS-CoV-2 but did not alter disease progression, viral kinetics or evolution in the PTM model. SIV-induced immunodeficiency alone may not be sufficient to drive the emergence of novel viral variants.
Databáze: MEDLINE