Poxviridae (taxid:10240)

Host-virus interaction

Adaptive immune response inhibition

The vaccinia virus A35R localizes to host endosomes and inhibits MHC class II antigen presentation . Additionally, the poxviral E3 ubiquitin-protein ligase LAP promotes ubiquitination and subsequent degradation of host MHC-I and CD4 molecules .

Apoptosis modulation

Several poxviral proteins are dedicated to the inhibition of host apoptosis. For example Myxoma virus M11L alters the pathway by preventing the conformational activation of host Bax at the mitochondria .
Vaccinia F1L functions both as a suppressor of proapoptotic Bcl-2 family of proteins and as an inhibitor of caspase-9 .
Molluscipoxviruses encode a viral FLICE-inhibitory protein (v-FLIP) that prevents apoptosis induced by death receptors .
FPV039 inhibits apoptosis by sequestering and inactivating multiple proapoptotic Bcl-2 proteins, including Bak and Bax .

Autophagy modulation

Vaccinia virus actively disrupts the cellular autophagy through a mechanism that involves aberrant LC3 lipidation and a direct conjugation between ATG12 and ATG3 .

Cell-cycle modulation

The myxomavirus Ankyrin repeat domain-containing protein M-T5 is an adapter of SKP1-containing E3 ubiquitin-protein ligases which mediate the ubiquitination and subsequent proteasomal degradation of host target proteins including CDKN1B. Disappearance of host CDKN1B correlates with cell cycle progression through the G0/G1 checkpoint .

NF-kappa-B modulation

The B14 protein from vaccinia virus functions by binding to the IKK complex via an interaction with IKK-beta and preventing the phosphorylation of IKK-beta on its activation loop. In turn, IKK-beta is not activated and fails to phosphorylate IkB-beta, leaving IkB-beta able to retain NF-kappa-B in the cytoplasm . MC159 protein from the molluscum contagiosum instead inhibits NF-kappa-B activation by interacting with the IkB kinase complex .

Innate immune response inhibition

Poxviruses inhibit the cascade leading to production of interferon-beta by mainly targeting the host IRF3 protein. For instance, vaccinia virus protein C6 inhibits IRF3 activation downstream of TBK1 .