Role of TRIM41 in antiviral defense against influenza and vesicular stomatitis virus

Abstract

TRIM41 is a member of TRIM family of host proteins. TRIM proteins are E3 ubiquitin ligase proteins and play important roles in various cellular functions like tumorigenesis, autophagy, innate, and intrinsic antiviral immunity. Structurally 3 domains of proteins are preserved throughout the family and the C-terminal domains are variable. TRIM41 is a protein that is ubiquitous and constitutively expressed in variety of cell types. N-terminal RING, B-BOX and Coiled Coil domains are conserved domains where as TRIM41 possesses a C- terminal SPRY domain. Our proteomics studies of host-viral protein interaction network revealed interaction between TRIM41 and nucleoprotein of Influenza A virus (IAV).We found that TRIM41 interacts with nucleoprotein of these Influenza A through its SPRY domain. Overexpression of TRIM41 in cells reduces the IAV infection whereas depletion of TRIM41 increases susceptibility of host cells to the infection. TRIM41 like all other TRIM proteins is a E3 ubiquitin ligase and it polyubiquitinates IAV nucleoprotein in-vitro and in cells. TRIM41 lacking E3 ligase activity fail to restrict viral infection indicating the importance of E3 ligase activity for TRIM41 in its antiviral function. During the study, TRIM41 was also identified as an inhibitor of vesicular stomatitis virus (VSV) infection. TRIM41 through its SPRY domain interacts with nucleoprotein of VSV. RING domain plays a crucial role in antiviral activity of TRIM41 against VSV. The interaction with TRIM41 leads to polyubiquitination and proteasomal degradation of VSV nucleoprotein. Taken together, TRIM41 is a host intrinsic immune protein that functions against IAV and VSV by targeting their nucleoprotein for polyubiquitination and subsequent proteasomal degradation.