Human Cytomegalovirus and Autoimmune Disease

Table 1

Immunomodulatory functions by HCMV.

Gene	Phenotype/suggested mechanism	Reference
T-cell responses
US2	Degrades MHC class I and II	[30, 31]
US3	Retention of MHC class I complexes, mislocalization of MHC class II	[32, 33]
US6	Inhibits the peptide transporter TAP	[34, 35]
US11	Degrades MHC class I	[36]
US8	Binds MHC class I heavy chains, function unknown	[37]
UL18	Inhibits MHC I interaction with the PLC	[38]
miR-US4-1	Targets Erap1	[39]
?	Disturbed interaction between MHC class I and the PLC	[40]
UL11	Interacts with CD45	[41]
NK and NKT cell responses
UL16	Intracellular retention of MICB and ULBP1 and 2	[42]
UL18	LIR-1 activation	[43]
UL40	Encodes a signal peptide for HLA-E	[44]
UL142	MICA and ULBP3 inhibition	[45, 46]
miR-UL112	MICB downregulation	[47]
UL83	Inhibition of NKp30	[48]
TRL11	Inhibition of CD16 activation	[49]
UL119-118; TRL11	Inhibition of CD16 activation	[49]
US10	Downregulates HLA-G	[50]
US2	Inhibits CD1d	[51]
Cytokines, chemokines, chemotaxis
US28	Chemokine receptor; promotes chemotaxis; potential chemokine trap	[52, 53]
US27	Enhancement of CXCR4 signaling	[54]
UL33	GPCR family; modulates CCR5 and CXCR4	[55]
UL111a	vIL-10; hIL-10-like functions	[56, 57]
UL111a	LAvIL10; downregulates MHC class II expression	[58]
UL146	vCXCL1, hCXCR1/hCXCR2-specific chemokine; promotes neutrophil chemotaxis	[59]
UL147	IL-8 similarity	[60]
UL21.5	Sequesters RANTES; binds CCL5 and prevents host cell signalling	[61]
UL128	Increases TNF𝛼 and IL-6 expression by PBMC; promotes PBMC migration	[62]
UL78	GPCR family member; modulates CCR5 and CXCR4	[55]
Modulation of IFN and TNF signaling
UL138	Upregulates TNF𝛼R1	[63, 64]
UL144	TNFR homolog, inhhibits T-cell prolif. via BTLA-4; induces CCL22	[65]
UL7	Inhibits inflammatory cytokine production	[66]
?	Jak1 degradation	[67]
?	STAT2 degradation	[68]
UL83	Suppresses type I IFN response and IRF3-induction	[69]
TRS1	Blocks PKR-mediated translation shut-off	[70]
UL126a	Inhibits OAS	[71]
UL123	Binds STAT2 and inhibits DNA binding; modulated phosphorylation state of IE1	[72]
UL122	Inhibiton of NFκB; inhibition of IFN𝛽 transcription	[73]
Apoptosis
UL37x1	Neutralizes Bax	[74]
UL36x1	Caspase-8 inhibitor	[75]
UL121/123	Inhibits apoptosis	[76]
Intrinsic immunity
UL123	Disruption of ND10	[77]
UL82	Daxx inhibitor	[78–80]