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

• Published in: PLoS pathogens Vol. 17; no. 7; p. e1009668
• Main Authors: Nomura, Takushi, Yamamoto, Hiroyuki, Nishizawa, Masako, Hau, Trang Thi Thu, Harada, Shigeyoshi, Ishii, Hiroshi, Seki, Sayuri, Nakamura-Hoshi, Midori, Okazaki, Midori, Daigen, Sachie, Kawana-Tachikawa, Ai, Nagata, Noriyo, Iwata-Yoshikawa, Naoko, Shiwa, Nozomi, Iida, Shun, Katano, Harutaka, Suzuki, Tadaki, Park, Eun-Sil, Maeda, Ken, Suzaki, Yuriko, Ami, Yasushi, Matano, Tetsuro
• Format: Journal Article
• Language: English
• Published: San Francisco Public Library of Science 19.07.2021; Public Library of Science (PLoS)
• Subjects: Analysis; Animals; Antibodies; Biology and life sciences; CD8 antigen; Coronaviruses; COVID-19; Disease transmission; Experiments; Infections; Lymph nodes; Lymphocytes; Lymphocytes T; Medicine and health sciences; Mucosa; Necropsy; Pharynx; Replication; Respiratory failure; Ribonucleic acid; RNA; Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; T cells; Viral diseases; Viral infections; Viruses; Japan
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1009668

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 10 5 or 10 6 TCID 50 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.