Grass carp TMEM33 promotes GCRV replication by targeting MAVS for degradation and suppressing host antiviral immune response

Abstract

Grass carp (Ctenopharyngodon idella) is a major freshwater aquaculture species in China. However, recurrent grass carp reovirus (GCRV) causes severe mortalities and significant economic damage to overall production. Thus, identifying critical regulators of antiviral immunity may provide promising targets for the prevention and control of viral infection. In this study, the transmembrane protein 33 (CiTMEM33) was cloned from grass carp, and its role in GCRV infection and host antiviral immune response was analyzed. We observed that CiTMEM33 is evolutionarily conserved among different species, and is robustly expressed in all tissues analyzed. Upon GCRV infection or poly(I:C) stimulation, the expression of CiTMEM33 was dynamically altered. Moreover, knocking down CiTMEM33 expression in cells significantly affected GCRV infection, while increasing its expression showed the opposite effect. Furthermore, CiTMEM33 attenuated the host antiviral response by blocking the IFN signaling pathway. Mechanistically, CiTMEM33 interacts with mitochondrial antiviral signaling protein (MAVS), promotes its degradation through ubiquitin–proteasome system, and inhibits MAVS-mediated IFN activation. Taken together, these results indicate that CiTMEM33 functions as a key negative regulator of antiviral immunity and represents a potential target for developing disease-resistant grass carp.

Keywords

Grass carp / TMEM33 / GCRV / Antiviral immune response / MAVS / Degradation

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The Author(s), under exclusive licence to Ocean University of China