Tyrosine dephosphorylation of STAT3 in SARS coronavirus‐infected Vero E6 cells

Severe acute respiratory syndrome (SARS) has become a global public health emergency. p38 mitogen‐activated protein kinase (MAPK) and its downstream targets are activated in SARS coronavirus (SARS‐CoV)‐infected Vero E6 cells and activation of p38 MAPK enhances the cytopathic effects of SARS‐CoV infection. In addition, weak activation of Akt cannot prevent SARS‐CoV infection‐induced apoptosis in Vero E6 cells. In the present study, we demonstrated that signal transducer and activator of transcription (STAT) 3, which is constitutively phosphorylated at tyrosine (Tyr)‐705 and slightly phosphorylated at serine (Ser)‐727 in Vero E6 cells, was dephosphorylated at Tyr‐705 on SARS‐CoV infection. In addition to phosphorylation of p38 MAPK in virus‐infected cells, other MAPKs, i.e., extracellular signal‐regulated kinase (ERK) 1/2 and c‐Jun N‐terminal kinase (JNK), were phosphorylated. Although inhibitors of ERK1/2 and JNK (PD98059 and SP600125) had no effect on phosphorylation status of STAT3, inhibitors of p38 MAPK (SB203580 and SB202190) partially inhibited dephosphorylation of STAT3 at Tyr‐705. Tyr‐705‐phosphorylated STAT3 was localized mainly in the nucleus in mock infected cells, whereas STAT3 disappeared from the nucleus in virus‐infected cells. As STAT3 acts as an activator of transcription in the nucleus, these results suggest that STAT3 lacks its activity on transcription in SARS‐CoV‐infected Vero E6 cells.