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Subacute SARS-CoV-2 replication can be controlled in the absence of CD8+ T cells in cynomolgus macaques.
- Source :
- PLoS Pathogens; 7/19/2021, Vol. 17 Issue 7, p1-16, 16p
- Publication Year :
- 2021
-
Abstract
- SARS-CoV-2 infection presents clinical manifestations ranging from asymptomatic to fatal respiratory failure. Despite the induction of functional SARS-CoV-2-specific CD8<superscript>+</superscript> T-cell responses in convalescent individuals, the role of virus-specific CD8<superscript>+</superscript> T-cell responses in the control of SARS-CoV-2 replication remains unknown. In the present study, we show that subacute SARS-CoV-2 replication can be controlled in the absence of CD8<superscript>+</superscript> T cells in cynomolgus macaques. Eight macaques were intranasally inoculated with 10<superscript>5</superscript> or 10<superscript>6</superscript> TCID<subscript>50</subscript> of SARS-CoV-2, and three of the eight macaques were treated with a monoclonal anti-CD8 antibody on days 5 and 7 post-infection. In these three macaques, CD8<superscript>+</superscript> T cells were undetectable on day 7 and thereafter, while virus-specific CD8<superscript>+</superscript> T-cell responses were induced in the remaining five untreated animals. Viral RNA was detected in nasopharyngeal swabs for 10–17 days post-infection in all macaques, and the kinetics of viral RNA levels in pharyngeal swabs and plasma neutralizing antibody titers were comparable between the anti-CD8 antibody treated and untreated animals. SARS-CoV-2 RNA was detected in the pharyngeal mucosa and/or retropharyngeal lymph node obtained at necropsy on day 21 in two of the untreated group but undetectable in all macaques treated with anti-CD8 antibody. CD8<superscript>+</superscript> T-cell responses may contribute to viral control in SARS-CoV-2 infection, but our results indicate possible containment of subacute viral replication in the absence of CD8<superscript>+</superscript> T cells, implying that CD8<superscript>+</superscript> T-cell dysfunction may not solely lead to viral control failure. Author summary: SARS-CoV-2 infection presents a wide spectrum of clinical manifestations ranging from asymptomatic to fatal respiratory failure. The determinants for failure in viral control and/or fatal disease progression have not been elucidated fully. Both acquired immune effectors, antibodies and CD8<superscript>+</superscript> T cells, are considered to contribute to viral control. However, it remains unknown whether a deficiency in either of these two arms is directly linked to failure in the control of SARS-CoV-2 replication. In the present study, to know the requirement of CD8<superscript>+</superscript> T cells for viral control after the establishment of infection, we examined the effect of CD8<superscript>+</superscript> cell depletion by monoclonal anti-CD8 antibody administration in the subacute phase on SARS-CoV-2 replication in cynomolgus macaques. Unexpectedly, our analysis revealed no significant impact of CD8<superscript>+</superscript> cell depletion on viral replication, indicating that subacute SARS-CoV-2 replication can be controlled in the absence of CD8<superscript>+</superscript> T cells. CD8<superscript>+</superscript> T-cell responses may contribute to viral control in SARS-CoV-2 infection, but this study suggests that CD8<superscript>+</superscript> T-cell dysfunction may not solely lead to viral control failure or fatal disease progression. [ABSTRACT FROM AUTHOR]
- Subjects :
- SARS-CoV-2
MACAQUES
T cells
ANTIBODY titer
VIRAL replication
INTESTINAL mucosa
Subjects
Details
- Language :
- English
- ISSN :
- 15537366
- Volume :
- 17
- Issue :
- 7
- Database :
- Complementary Index
- Journal :
- PLoS Pathogens
- Publication Type :
- Academic Journal
- Accession number :
- 151473490
- Full Text :
- https://doi.org/10.1371/journal.ppat.1009668