Subacute SARS-CoV-2 replication can be controlled in the absence of CD8+ T cells in cynomolgus macaques.
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 repli...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2021-07-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1009668 |
| _version_ | 1819141370399424512 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Takushi Nomura |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-22T11:53:22Z |
| format | Article |
| id | doaj.art-71e0a6a0280f4871b48e28d8d1432054 |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-12-22T11:53:22Z |
| publishDate | 2021-07-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-71e0a6a0280f4871b48e28d8d14320542022-12-21T18:26:54ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742021-07-01177e100966810.1371/journal.ppat.1009668Subacute SARS-CoV-2 replication can be controlled in the absence of CD8+ T cells in cynomolgus macaques.Takushi NomuraHiroyuki YamamotoMasako NishizawaTrang Thi Thu HauShigeyoshi HaradaHiroshi IshiiSayuri SekiMidori Nakamura-HoshiMidori OkazakiSachie DaigenAi Kawana-TachikawaNoriyo NagataNaoko Iwata-YoshikawaNozomi ShiwaShun IidaHarutaka KatanoTadaki SuzukiEun-Sil ParkKen MaedaYuriko SuzakiYasushi AmiTetsuro MatanoSARS-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.https://doi.org/10.1371/journal.ppat.1009668 |
| spellingShingle | 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 Subacute SARS-CoV-2 replication can be controlled in the absence of CD8+ T cells in cynomolgus macaques. PLoS Pathogens |
| title | Subacute SARS-CoV-2 replication can be controlled in the absence of CD8+ T cells in cynomolgus macaques. |
| title_full | Subacute SARS-CoV-2 replication can be controlled in the absence of CD8+ T cells in cynomolgus macaques. |
| title_fullStr | Subacute SARS-CoV-2 replication can be controlled in the absence of CD8+ T cells in cynomolgus macaques. |
| title_full_unstemmed | Subacute SARS-CoV-2 replication can be controlled in the absence of CD8+ T cells in cynomolgus macaques. |
| title_short | Subacute SARS-CoV-2 replication can be controlled in the absence of CD8+ T cells in cynomolgus macaques. |
| title_sort | subacute sars cov 2 replication can be controlled in the absence of cd8 t cells in cynomolgus macaques |
| url | https://doi.org/10.1371/journal.ppat.1009668 |
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