tetano
Editor, Senior Moderator
Antimicrob Agents Chemother
. 2020 Nov 30;AAC.01825-20.
doi: 10.1128/AAC.01825-20. Online ahead of print.
Efficacy of a cap-dependent endonuclease inhibitor and neuraminidase inhibitors against H7N9 highly pathogenic avian influenza virus causing severe viral pneumonia in cynomolgus macaques
Saori Suzuki[SUP] 1 [/SUP], Cong Thanh Nguyen[SUP] 1 [/SUP], Ayako Ogata-Nakahara[SUP] 1 [/SUP], Akihiro Shibata[SUP] 2 [/SUP], Hiroyuki Osaka[SUP] 2 [/SUP], Hirohito Ishigaki[SUP] 1 [/SUP], Masatoshi Okamatsu[SUP] 3 [/SUP], Yoshihiro Sakoda[SUP] 3 4 [/SUP], Hiroshi Kida[SUP] 4 5 6 [/SUP], Kazumasa Ogasawara[SUP] 1 [/SUP], Yasushi Itoh[SUP] 7 [/SUP]
Affiliations
Abstract
H7N9 highly pathogenic avian influenza virus (HPAIV) infection in a human was first reported in 2017. A/duck/Japan/AQ-HE29-22/2017 (H7N9) (Dk/HE29-22) found in imported duck meat at an airport in Japan possessed hemagglutinin with a multi-basic cleavage site, indicating high pathogenicity in chickens as in the case of other H7 HPAIVs. In the present study, we examined the pathogenicity of Dk/HE29-22 and the effectiveness of a cap-dependent endonuclease inhibitor (baloxavir) and neuraminidase inhibitors (oseltamivir and zanamivir) against infection with this strain in a macaque model (n = 3 for each group). All of the macaques infected with Dk/HE29-22 showed severe signs of disease and pneumonia even after the virus had disappeared from lung samples. Virus titers in macaques treated with baloxavir were significantly lower than those in the other treated groups. After infection, levels of IFN-α and IFN-β in the blood of macaques in the baloxavir group were the highest among the groups, whereas levels of TNF-α and IL-13 were slightly increased in the untreated group. In addition, immune checkpoint proteins including PD-1 and TIGIT were expressed at high levels in the untreated group, especially in one macaque that showed severe signs of disease, indicating that negative feedback responses against vigorous inflammation may contribute to disease progression. In the group treated with baloxavir, the percentages of PD-1, CTLA-4, and TIGIT-positive T lymphocytes were lower than those in the untreated group, indicating that reduction in virus titers may prevent expression of immune checkpoint molecules from downregulation of T cell responses.
. 2020 Nov 30;AAC.01825-20.
doi: 10.1128/AAC.01825-20. Online ahead of print.
Efficacy of a cap-dependent endonuclease inhibitor and neuraminidase inhibitors against H7N9 highly pathogenic avian influenza virus causing severe viral pneumonia in cynomolgus macaques
Saori Suzuki[SUP] 1 [/SUP], Cong Thanh Nguyen[SUP] 1 [/SUP], Ayako Ogata-Nakahara[SUP] 1 [/SUP], Akihiro Shibata[SUP] 2 [/SUP], Hiroyuki Osaka[SUP] 2 [/SUP], Hirohito Ishigaki[SUP] 1 [/SUP], Masatoshi Okamatsu[SUP] 3 [/SUP], Yoshihiro Sakoda[SUP] 3 4 [/SUP], Hiroshi Kida[SUP] 4 5 6 [/SUP], Kazumasa Ogasawara[SUP] 1 [/SUP], Yasushi Itoh[SUP] 7 [/SUP]
Affiliations
- PMID: 33257455
- DOI: 10.1128/AAC.01825-20
Abstract
H7N9 highly pathogenic avian influenza virus (HPAIV) infection in a human was first reported in 2017. A/duck/Japan/AQ-HE29-22/2017 (H7N9) (Dk/HE29-22) found in imported duck meat at an airport in Japan possessed hemagglutinin with a multi-basic cleavage site, indicating high pathogenicity in chickens as in the case of other H7 HPAIVs. In the present study, we examined the pathogenicity of Dk/HE29-22 and the effectiveness of a cap-dependent endonuclease inhibitor (baloxavir) and neuraminidase inhibitors (oseltamivir and zanamivir) against infection with this strain in a macaque model (n = 3 for each group). All of the macaques infected with Dk/HE29-22 showed severe signs of disease and pneumonia even after the virus had disappeared from lung samples. Virus titers in macaques treated with baloxavir were significantly lower than those in the other treated groups. After infection, levels of IFN-α and IFN-β in the blood of macaques in the baloxavir group were the highest among the groups, whereas levels of TNF-α and IL-13 were slightly increased in the untreated group. In addition, immune checkpoint proteins including PD-1 and TIGIT were expressed at high levels in the untreated group, especially in one macaque that showed severe signs of disease, indicating that negative feedback responses against vigorous inflammation may contribute to disease progression. In the group treated with baloxavir, the percentages of PD-1, CTLA-4, and TIGIT-positive T lymphocytes were lower than those in the untreated group, indicating that reduction in virus titers may prevent expression of immune checkpoint molecules from downregulation of T cell responses.