SARS-CoV MAPK PERTURBATION

Serine/threonine protein kinases MAPKs are activated following several different environmental stimuli, such as DNA damage, heat shock or pro-inflammatory cytokines. Typically MAPKs, by phosphorylating their protein substrates, regulate numerous crucial cellular processes such as proliferation, apoptosis, and immune response. This pathway describes the activation of p38, ERK, and JNK signalling occurring during Human coronavirus proteins (HCoV) infection. Activated p38 can directly or indirectly phosphorylates a wide variety of substrate proteins, including important transcription factors such as CREB, ATF2, AP1 and CHOP. Several studies have demonstrated p38 activation in Vero E6 cells infected with SARS-CoV. Similar to p38, phosphorylation of ERK and upstream kinases MKK1/2 has been observed in A549 and Vero E6 cells upon SARS-CoV infection. Likewise, phosphorylation of JNK and its upstream kinases MKK4 and MKK7 was observed in Vero E6 cells infected with SARS-CoV. Recent studies have demonstrated the involvement of Growth Factor Receptors signalling in the activation of MAPK signalling cascade during HCoV infection. This pathway also shows how the ectopic expression of HCoV proteins, such as E, N, 3a, 3b, 7a can promote p38, JNK and ERK1/2 activation.