Interaction between NS1 and Cellular MAVS Contributes to NS1 Mitochondria Targeting

Author:

Tseng Yeu-Yang,Kuan Chih-Ying,Mibayashi Masaki,Chen Chi-Jene,Palese PeterORCID,Albrecht Randy A.ORCID,Hsu Wei-LiORCID

Abstract

Influenza A virus nonstructural protein 1 (NS1) plays an important role in evading host innate immunity. NS1 inhibits interferon (IFN) responses via multiple mechanisms, including sequestering dsRNA and suppressing retinoic acid-inducible gene I (RIG-I) signaling by interacting with RIG-I and tripartite motif-containing protein 25 (TRIM25). In the current study, we demonstrated the mitochondrial localization of NS1 at the early stage of influenza virus infection. Since NS1 does not contain mitochondria-targeting signals, we suspected that there is an association between the NS1 and mitochondrial proteins. This hypothesis was tested by demonstrating the interaction of NS1 with mitochondrial antiviral-signaling protein (MAVS) in a RIG-I-independent manner. Importantly, the association with MAVS facilitated the mitochondrial localization of NS1 and thereby significantly impeded MAVS-mediated Type I IFN production.

Funder

Ministry of Science and Technology, Taiwan

National Institutes of Health

Publisher

MDPI AG

Subject

Virology,Infectious Diseases

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