Subacute SARS-CoV-2 replication can be controlled in the absence of CD8+ T cells in cynomolgus macaques.

Autor: Takushi Nomura, Hiroyuki Yamamoto, Masako Nishizawa, Trang Thi Thu Hau, Shigeyoshi Harada, Hiroshi Ishii, Sayuri Seki, Midori Nakamura-Hoshi, Midori Okazaki, Sachie Daigen, Ai Kawana-Tachikawa, Noriyo Nagata, Naoko Iwata-Yoshikawa, Nozomi Shiwa, Shun Iida, Harutaka Katano, Tadaki Suzuki, Eun-Sil Park, Ken Maeda, Yuriko Suzaki, Yasushi Ami, Tetsuro Matano
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: PLoS Pathogens, Vol 17, Iss 7, p e1009668 (2021)
Druh dokumentu: article
ISSN: 1553-7366
1553-7374
DOI: 10.1371/journal.ppat.1009668
Popis: SARS-CoV-2 infection presents clinical manifestations ranging from asymptomatic to fatal respiratory failure. Despite the induction of functional SARS-CoV-2-specific CD8+ T-cell responses in convalescent individuals, the role of virus-specific CD8+ 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+ T cells in cynomolgus macaques. Eight macaques were intranasally inoculated with 105 or 106 TCID50 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+ T cells were undetectable on day 7 and thereafter, while virus-specific CD8+ 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+ 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+ T cells, implying that CD8+ T-cell dysfunction may not solely lead to viral control failure.
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