Table 5 Pathogenic proteins that target TRAFs

Function as DUBs of TRAFs

Lb(pro) of foot-and-mouth disease virus

TRAF3, TRAF6

Deubiquitinates TRAF3 and 6 to inhibit RIG-I signaling

[21]

X protein (HBx) of hepatitis B virus

TRAF3

Deubiquitinates TRAF3 to inhibit RIG-I signaling

[240]

YopJ of the Gram- bacterium Yersinia pestis

TRAF3, TRAF6

Deubiquitinates TRAF3 and 6 to inhibit TLR signaling

[241]

Disrupt the formation of TRAF signaling complex

Gn protein of NY-1 hantavirus

TRAF3

Disrupts the interaction of TRAF3 and TBK1-IKKε

[242]

M protein of severe acute respiratory syndrome (SARS) coronavirus

TRAF3

Prevents the formation of TRAF3-TBK1-IKKε complex

[243]

A52R of vaccinia virus

TRAF6

Disrupts the signaling complex of TRAF6 and IRAK2

[244]

K7 of vaccinia virus

TRAF6

Disrupts the signaling complex of TRAF6 and IRAK2

[20]

Usurp TRAFs for viral signaling

LMP1 of Epstein-Barr virus

TRAF1, 2, 3, 5, 6

Sequesters cellular TRAF3, and usurps TRAF1, 2, 3, 5

[245–249]

and 6 to mimic constitutively activated CD40 signaling

BRRF1 lytic gene product (Na) of Epstein-Barr virus

TRAF2

Utilizes TRAF2 for JNK activation and lytic gene

[254]

expression

v-FLIP of Kaposi’s sarcoma herpesvirus (human herpesvirus 8)

TRAF2, TRAF3

Recruits TRAF2 and 3 to activate NF-κB and JNK, and

[255]

to induce cell survival in primary effusion lymphomas

U(L)37 tegument protein of the herpes simplex virus (HSV)

TRAF6

Activates TRAF6 and NF-κB to induce IL-8 expression

[256]

Modify TRAF signaling complex

MC159 of human molluscum contagiosum virus

TRAF2, TRAF3

Recruits TRAF2 and 3 to Fas signaling complex

[250]

and inhibits Fas-induced apoptosis

Induce miRNAs to target TRAFs

Tat protein of HIV-1

TRAF3

Up-regulates miR-32 that directly targets TRAF3

[251]

VSV

TRAF6

Up-regulates miR-146a that targets TRAF6 and IRAK1

[252]