TABLE 3.
Pathogenic mechanisms of herpesvirus infectionsa
| Immune response | Herpesviruses | Viral factor/cellular targets | Effect |
|---|---|---|---|
| Innate immunity (cytosolic sensing of nucleic acids) | HSV-1, HSV-2 | UL37 (RIG-I, cGAS, TRAF6); ICP0 (IFI16, STING, p50); US3 (IRF3, p65); ICP27 and ICP24 (TBK-1); VP16 (CBP) | Downregulation (except TRAF6) |
| HCMV | pUL83 (IFI16, cGAS, IRF3, p50-p65); UL31 (cGAS); pUL82 (STING); US9 (MAVS, STING, IRF3); IE86 (p50-p65) | Downregulation | |
| KSHV, EBV | RTA (IRF3, IRF7, p65); ORF36 (IRF3); dUTPase vGAT/ORF75 (RIG-I); ORF63 (RIG-I); ORF52 (cGAS); LANA (cGAS); vIRF1 (STING, IRF3) | Downregulation | |
| Adaptive immunity (antigen presentation) | HSV-1, HSV-2 | ICP47: inhibition of TAP-mediated antigen presentation US3: MHC-I and CD1d downregulation from cell surface | Downregulation of antigen presentation |
| HCMV | US2, US10, and US11: MHC-I retention or degradation US6: inhibition of TAP-mediated antigen presentation US3 and UL82: MHC-I retention and MHC-II mislocalization UL83 and US4–1: generation of antigenic peptides | Downregulation of antigen presentation | |
| KSHV, EBV | K3 and K5 (KSHV): MHC-I degradation | Downregulation of antigen presentation | |
| Cytokine/chemokine (production and signaling) | HSV-1, HSV-2 | Vhs: mRNA degradation to avoid cytokine production | Immune suppression |
| HCMV | UL11: induction of IL-10 via CD45 vIL-10: mimicry of cellular IL-10 US27, US28, UL33, and UL78: hijacking of IL-8-mediated chemotaxis |
Immune suppression | |
| KSHV, EBV | vGPCR: hijacking of IL-8-mediated chemotaxis vIL-6: stimulation of B cell proliferation/viral dissemination microRNA: IL-6 and IL-10 induction |
Immune suppression (IL-8 and IL10) and activation (IL-6) |
Abbreviations: CBP, CREB-binding protein; CD1b, cluster of differentiation 1b; cGAS, cyclic GMP-AMP synthase; dUTPase, deoxyuridine triphosphatase; EBV, Epstein-Barr virus; GPCR, G protein-coupled receptor; HCMV, human cytomegalovirus; HSV-1 and HSV-2, herpes simplex virus-1 and −2; ICP, infected cell protein; IFI16, gamma-interferon-inducible protein Ifi-16; IL, interleukin; IE86, immediate early 86 kDalton protein; IRF, interferon regulatory factor; KSHV, Kaposi sarcoma-associated human herpesvirus; LANA, latency-associated nuclear antigen; MAVS, mitochondrial antiviral-signaling; MHC, major histocompatibility complex; ORF, open reading frame; RIG-I, retinoic acid-inducible gene I; RTA, replication and transcription activator; STING, stimulator of interferon genes; TAP, transporter associated with antigen processing; TBK1, TANK-binding kinase 1; TRAF6, TNF receptor associated factor 6; UL, unique long; US, unique short; vGAT, viral glutamine amidotransferase; vGPCR, viral G protein-coupled receptor; Vhs, virion host shutoff; vIFR, viral interferon regulatory factor; vIL, viral interleukin; VP, virion protein.