PROLONGED SARS-CoV-2 VIRAL BURDEN IN SIV-SARS-CoV-2 COINFECTED MACAQUES
Topics in Antiviral Medicine
; 31(2):117, 2023.
Article
in English
| EMBASE | ID: covidwho-2314619
ABSTRACT
Background:
Individuals living with HIV are at increased risk of morbidity and mortality from COVID-19. Furthermore, SARS-CoV-2 infection in immunocompromised HIV infected individuals poses a risk to prolonged infection and viral shedding and the emergence of new variants of concern (VOCs). Using the SIV macaque model for AIDS, we are investigating the hypothesis that immune dysfunction during HIV infection will prolong SARSCoV- 2 viral infection, promote enhanced COVID-19 disease, and accelerate viral evolution. Here, we report the impact of SIV-CoV-2 co-infection on immune responses and pathogenesis. Method(s) Eight female rhesus macaques (aged 7-15 years, 5.5-9.9kg) were infected with SIVmac251 via low dose intravaginal challenge and then inoculated with 6.5x105 TCID50/mL SARS-CoV-2 (WA-1) at 17-34 weeks post-SIV infection via combined intranasal and intratracheal routes. Blood, bronchoalveolar lavage (BAL), stool, and nasal, oral, and rectal swabs were collected pre-infection through 14 days post-infection (DPI) to measure immune responses and viremia. ELISAs, ELISPOT, qRT-PCR, lung pathology, cytokine multiplex, and virus neutralization assays were performed to measure viral loads, pathogenesis, and immune responses. Result(s) Three days post-SARS-CoV-2 infection, we observed a transient decrease in CD4 counts, but there were no changes in clinical symptoms or plasma SIV viral loads. However, SARS-CoV-2 replication persisted in the upper respiratory tract, but not the lower respiratory tract. In addition, SARS-CoV-2 IgG seroconversion was delayed and antigen-specific T-cell responses were dampened. Notably, viral RNA levels in nasal swabs were significantly higher 7-14 DPI in SIV+ compared to previously published results using the same SARS-CoV-2 challenge virus in SIV- rhesus (PMCID PMC8462335, PMC8829873). In addition, SIV/CoV-2 co-infected animals exhibited elevated levels of myeloperoxidase (MPO), a marker of neutrophil activation and increased lung inflammation. Conclusion(s) Here we provide evidence for the utility of the rhesus macaque in modeling human HIV-SARS-CoV-2 co-infection. Our results suggest that immunosuppression during SIV infection impairs de novo generation of anti-SARS-CoV-2 immunity, that may contribute to prolonged SARS-CoV-2 viral shedding, increased transmission windows, altered disease pathogenesis, and lower protection against subsequent SARS-CoV-2 exposures. Studies in progress will determine if SARS-CoV-2 viral evolution is accelerated in SIV-infected macaques.
acquired immune deficiency syndrome; adolescent; animal experiment; animal model; animal tissue; CD4 lymphocyte count; coinfection; conference abstract; coronavirus disease 2019; enzyme linked immunospot assay; feces; female; gene expression; Human immunodeficiency virus infection; immune response; immunopathology; immunosuppressive treatment; leukocyte activation; low drug dose; lower respiratory tract; lung disease; lung lavage; macaque model; nonhuman; nose smear; pneumonia; protein expression; rectal swab; rhesus monkey; SARS coronavirus 2 immunology test kit; seroconversion; Severe acute respiratory syndrome coronavirus 2; Simian immunodeficiency virus; T lymphocyte; tcid50; upper respiratory tract; viral evolution; viremia; virus load; virus neutralization test; virus shedding; virus transmission; antigen; cytokine; endogenous compound; myeloperoxidase; virus RNA
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Collection:
Databases of international organizations
Database:
EMBASE
Language:
English
Journal:
Topics in Antiviral Medicine
Year:
2023
Document Type:
Article
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