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Subacute SARS-CoV-2 replication can be controlled in the absence of CD8+ T cells in cynomolgus macaques.
PLoS Pathog. 2021 07; 17(7):e1009668.PP

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+ 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.

Authors+Show Affiliations

AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan.AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan.AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan.AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan.AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan.AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan.AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan.AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan.AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan.AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan.AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan. Institute of Medical Science, University of Tokyo, Tokyo, Japan. Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto, Japan.Department of Pathology, National Institute of Infectious Diseases, Tokyo, Japan.Department of Pathology, National Institute of Infectious Diseases, Tokyo, Japan.Department of Pathology, National Institute of Infectious Diseases, Tokyo, Japan.Department of Pathology, National Institute of Infectious Diseases, Tokyo, Japan.Department of Pathology, National Institute of Infectious Diseases, Tokyo, Japan.Department of Pathology, National Institute of Infectious Diseases, Tokyo, Japan.Department of Veterinary Science, National Institute of Infectious Diseases, Tokyo, Japan.Department of Veterinary Science, National Institute of Infectious Diseases, Tokyo, Japan.Management Department of Biosafety, Laboratory Animal, and Pathogen Bank, National Institute of Infectious Diseases, Tokyo, Japan.Management Department of Biosafety, Laboratory Animal, and Pathogen Bank, National Institute of Infectious Diseases, Tokyo, Japan.AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan. Institute of Medical Science, University of Tokyo, Tokyo, Japan. Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto, Japan.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

34280241

Citation

Nomura, Takushi, et al. "Subacute SARS-CoV-2 Replication Can Be Controlled in the Absence of CD8+ T Cells in Cynomolgus Macaques." PLoS Pathogens, vol. 17, no. 7, 2021, pp. e1009668.
Nomura T, Yamamoto H, Nishizawa M, et al. Subacute SARS-CoV-2 replication can be controlled in the absence of CD8+ T cells in cynomolgus macaques. PLoS Pathog. 2021;17(7):e1009668.
Nomura, T., Yamamoto, H., Nishizawa, M., Hau, T. T. T., Harada, S., Ishii, H., Seki, S., Nakamura-Hoshi, M., Okazaki, M., Daigen, S., Kawana-Tachikawa, A., Nagata, N., Iwata-Yoshikawa, N., Shiwa, N., Iida, S., Katano, H., Suzuki, T., Park, E. S., Maeda, K., ... Matano, T. (2021). Subacute SARS-CoV-2 replication can be controlled in the absence of CD8+ T cells in cynomolgus macaques. PLoS Pathogens, 17(7), e1009668. https://doi.org/10.1371/journal.ppat.1009668
Nomura T, et al. Subacute SARS-CoV-2 Replication Can Be Controlled in the Absence of CD8+ T Cells in Cynomolgus Macaques. PLoS Pathog. 2021;17(7):e1009668. PubMed PMID: 34280241.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Subacute SARS-CoV-2 replication can be controlled in the absence of CD8+ T cells in cynomolgus macaques. AU - Nomura,Takushi, AU - Yamamoto,Hiroyuki, AU - Nishizawa,Masako, AU - Hau,Trang Thi Thu, AU - Harada,Shigeyoshi, AU - Ishii,Hiroshi, AU - Seki,Sayuri, AU - Nakamura-Hoshi,Midori, AU - Okazaki,Midori, AU - Daigen,Sachie, AU - Kawana-Tachikawa,Ai, AU - Nagata,Noriyo, AU - Iwata-Yoshikawa,Naoko, AU - Shiwa,Nozomi, AU - Iida,Shun, AU - Katano,Harutaka, AU - Suzuki,Tadaki, AU - Park,Eun-Sil, AU - Maeda,Ken, AU - Suzaki,Yuriko, AU - Ami,Yasushi, AU - Matano,Tetsuro, Y1 - 2021/07/19/ PY - 2021/05/21/received PY - 2021/07/06/accepted PY - 2021/07/29/revised PY - 2021/7/20/pubmed PY - 2021/8/6/medline PY - 2021/7/19/entrez SP - e1009668 EP - e1009668 JF - PLoS pathogens JO - PLoS Pathog VL - 17 IS - 7 N2 - 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. SN - 1553-7374 UR - https://www.unboundmedicine.com/medline/citation/34280241/Subacute_SARS-CoV-2_replication_can_be_controlled_in_the_absence_of_CD8+_T_cells_in_cynomolgus_macaques. L2 - https://dx.plos.org/10.1371/journal.ppat.1009668 DB - PRIME DP - Unbound Medicine ER -