Cellular Deubiquitylating Enzyme: A Regulatory Factor of Antiviral Innate Immunity

Abstract

Deubiquitylating enzymes (DUBs) are proteases that crack the ubiquitin code from ubiquitylated substrates to reverse the fate of substrate proteins. Recently, DUBs have been found to mediate various cellular biological functions, including antiviral innate immune response mediated by pattern-recognition receptors (PRRs) and NLR Family pyrin domain containing 3 (NLRP3) inflammasomes. So far, many DUBs have been identified to exert a distinct function in fine-tuning antiviral innate immunity and are utilized by viruses for immune evasion. Here, the recent advances in the regulation of antiviral responses by DUBs are reviewed. We also discussed the DUBs-mediated interaction between the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and antiviral innate immunity. The understanding of the mechanisms on antiviral innate immunity regulated by DUBs may provide therapeutic opportunities for viral infection.

Pellino Proteins in Viral Immunity and Pathogenesis

“…Viruses extensively deploy immune evasion strategies to avoid detection by innate sensors and prevent activation of the inflammasome, reviewed in detail elsewhere [ 38 , 42 , 43 , 44 , 45 , 46 , 47 , 48 ]. During evolution, apparent redundancies have emerged as fail safes to ensure protective immunity even in the presence of highly effective microbial immune evasion mechanisms.…”

“…For example, mice deficient in the two inflammasome executioner proteases, caspase-1 and caspase-11, appear to develop normal protective immunity against HSV-1, as evidenced by their viral dissemination being on par with wild-type mice [ 49 ]. While several viral immune evasion mechanisms have been identified involving Pellino-activated NLRP3 and ASC [ 38 , 42 , 43 , 44 , 45 ], specific viral targeting of one or more of the Pellino proteins in these processes has not been examined. However, an unrelated direct viral immune evasion mechanism has been identified in the Melanoplus sanguinipes entomopoxvirus (MsEPV) [ 50 ].…”