Early cellular events induced by Sindbis virus via CD11b support viral infection

Sindbis virus (SINV) is an expanding arbovirus that causes human diseases characterized by dysregulation of inflammation response and immune response. Interaction of SINV with host factors is pivotal for establishment of infection. As an adhesion and signaling molecule with multiple biological functions, CD11b is regarded as a potential target for clinical therapy for some diseases. This study explored roles of CD11b in signaling events and cell response at early stages of SINV infection. SINV could establish a productive infection in human neuroblastoma SH-SY5Y cells. SINV infection inhibited FAK and TSC2 signaling but activated kinase cascades of AKT and ERK signaling pathways. SINV infection promoted mRNA expression of unfolded protein response components ATF6 and CHOP, inflammatory cytokine IL-11, and antiviral protein ISG15, accompanied by remarkable promotion of CD11b mRNA expression. Importantly, CD11b knockdown not only markedly decreased SINV replication but also significantly reduced the ATF6, CHOP, and IL-11 expression, coupled with impairment of the FAK, TSC2, AKT, and ERK signaling pathways. These early cellular events induced by SINV via CD11b are implicated in SINV replication and pathogenicity, suggesting CD11b may be a potential target for combating SINV infection, pending in vivo validation. • SINV infection increased CD11b expression. • CD11b knockdown decreased SINV replication. • CD11b knockdown reduced ATF6, CHOP, and IL-11 expression induced by SINV infection. • CD11b knockdown impaired FAK, TSC2, AKT, and ERK signaling pathways during SINV infection.