Transmissible gastroenteritis virus (TGEV) is an important swine enteric coronavirus causing viral
diarrhea in pigs of all ages. Currently, the development of
antiviral agents targeting host
proteins to combat
viral infection has received great attention. The
heat shock protein 90 (HSP90) is a critical host factor and has important regulatory effects on the
infection of various viruses. However, its roles in porcine
coronavirus infection remain unclear. In this study, the effect of HSP90 on TGEV
infection was evaluated. In addition, the influence of its inhibitor VER-82576 on proinflammatory
cytokine (IL-6,
IL-12, TNF-α, CXCL10, and CXCL11) production induced by TGEV
infection was further analyzed. The results showed that the knockdown of HSP90AB1 and HSP90 inhibitor VER-82576 treatment resulted in a reduction in TGEV M gene
mRNA levels, the N
protein level, and virus titers in a dose-dependent manner, while the knockdown of HSP90AA1 and
KW-2478 treatment had no significant effect on TGEV
infection. A time-of-addition assay indicated that the inhibitory effect of VER-82576 on TGEV
infection mainly occurred at the early stage of viral replication. Moreover, the TGEV-induced upregulation of proinflammatory
cytokine (IL-6,
IL-12, TNF-α, CXCL10, and CXCL11) expression was significantly inhibited by VER-82576. In summary, these findings indicated that HSP90AB1 is a host factor enhancing TGEV
infection, and the HSP90 inhibitor VER-82576 could reduce TGEV
infection and proinflammatory
cytokine production, providing a new perspective for TGEV
antiviral drug target design.