Post-translational modifications as a key mechanism for herpes simplex virus type I evasion of host innate immunity

Figures

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  FIGURE 1. The innate immune response is activates by the entry of HSV-1 into host cells. HSV-1 is recognized by PRRs, which trigger a signaling cascade that leads to the production of IFNs and cytokines. The entry of HSV-1 into the cell involves both the TLR and non-TLR pathways. Key viral DNA sensors include TLR9, cGAS, IFI16, and DAI, while viral RNA sensors include TLR3, MDA5, PKR and RIG-I. During viral attachment and entry, multiple virus-recognizing receptors detect viral components and initiate innate immune responses. Created with BioRender.com.

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  FIGURE 2. HSV-1 Us3 protein inhibits the host immune response by phosphorylating host proteins via its kinase activity. Following HSV-1 infection, host cells detect the viral nucleic acid sequences through various pathways, triggering the intrinsic antiviral immune response to combat viral proliferation and eliminate infected cells. The Us3 protein encoded by HSV-1 disrupts signal transmission in these pathways by phosphorylating key intermediate proteins, including IRF3 and RelA, thereby suppressing the host’s antiviral response. Created with BioRender.com.

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  FIGURE 3. HSV-1 ICP0 protein inhibits the host immune response by degrading host proteins through the ubiquitin-proteasome pathway. Upon entering the host cells, HSV-1 uses the host’s cellular machinery to synthesize the key immediate-early protein ICP0. Through its E3 ligase activity, ICP0 mediates the ubiquitin-dependent degradation of key immune pathway protein, such as IFI16 and MOCR3, effectively suppressing the host’s antiviral response. Figure created with BioRender.com.

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  FIGURE 4. HSV-1 UL37 protein deamidates host proteins to inhibit immune pathways. UL37, a capsid protein encoded by HSV-1 with deamidase activity, inhibits host antiviral immune responses by targeting key viral recognition sensors. Within host cells, UL37 deamidates cGAS and RIG-I, preventing the recognition of HSV-1 viral nucleic acids and effectively suppressing host-associated antiviral immune responses. Created with BioRender.com.