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, possesses a
hemagglutinin with a multibasic 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
interferon alpha and beta (IFN-α and IFN-β) in the blood of macaques in the
baloxavir group were the highest among the groups, whereas levels of
tumor necrosis factor alpha (TNF-α) and
interleukin 13 (IL-13) were slightly increased in the untreated group. In addition,
immune checkpoint proteins, including programmed death 1 (PD-1) and T cell immunoreceptor with Ig and ITIM domains (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.