Page 14 - O. Microbiology

[O. Microbiology-15]

Identification of crucial residues for interaction between

viperin and human cytomegalovirus protein vMIA

Jeong Jin Kim¹, Jun-Young Seo¹˙*

¹Severance Biomedical Science Institute, Brain Korea 21 PLUS Project for Medical Science, Yonsei University

College of Medicine, Seoul 03722, Republic of Korea

Viperin is a multifunctional interferon-inducible protein that is directly induced in cells by human cytomegalovirus
(HCMV) infection. Viperin re-localizes from ER to the mitochondria through interaction with HCMV protein vMIA

during viral infection. There, viperin mediates modulation of cellular lipid metabolism to enhance viral infectivity.

Mitochondrial targeting of viperin determines the efficiency of viral replication. Nevertheless, it is unknown which
residues are crucial for the interaction of viperin and vMIA. Here, we show that the N-terminal domain (aa 1-42) of
viperin and a single cysteine residue (aa 44) of vMIA are necessary for the interaction between these two proteins.

Interestingly, the N-terminal domain of mouse viperin which is structurally similar to human viperin, is also required
for interaction with vMIA, indicating that the structure rather than the sequence of the N-terminal domain of viperin

is important for the interaction with vMIA. The recombinant HCMV expressing a cysteine mutant of vMIA causes
mislocalization of viperin during viral infection, resulting in reduction of lipogenesis and viral replication. Therefore,

our data suggest that the interacting residues of these two proteins are potential therapeutic targets for HCMV-
associated diseases.