Figure 6.

HSVs interfere with dendritic cell function. Dendritic cells (DCs) are susceptible to HSV-1 and HSV-2 infection. (A) Upon infection with HSV, the host protein CYTIP is degraded, which causes the upregulation of LFA-1 and reduces the capacity of DCs to migrate to draining lymph nodes and activate T cells. (B) HSV infection hampers the capacity of DCs to present virus-derived antigens to T cells on MHC-I molecules by interfering with the activity of transporters associated with antigen presentation (TAP proteins). Inhibition of TAPs is mediated by the viral protein ICP47. (C) HSVs elicit apoptosis in DCs through the downregulation of c-FLIP, a potent anti-apoptotic protein, which is directed to the proteasome during infection of these cells. (D) HSV infection hampers the activity of the autophagosome, which has been reported to reduce antigen presentation to CD8⁺ T cells. (E) CD80 and CD86 are co-stimulatory molecules that are commonly upregulated during infection, and along with MHC-peptide complexes enable DCs to activate T cells. HSV inhibits the expression of CD80 and CD86 on the DC surface thanks to the viral proteins γ34.5. The viral protein ICP22 also inhibits the expression of CD80 on the cell surface. (F) HSV infection inhibits inducible nitric oxide synthase (iNOS) in DCs through the downregulation of caveolin-1, which will reduce the antiviral capacity of these cells. Black lines show cellular processes. Red lines show processes modulated by HSVs.