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The host cellular protein Ndufaf4 interacts with the vesicular stomatitis virus M protein and affects viral propagation

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Abstract

Vesicular stomatitis virus (VSV) is an archetypal member of Mononegavirales which causes important diseases in cattle, horses and pigs. The matrix protein (M) of VSV plays critical roles in the replication, assembly/budding and pathogenesis of VSV. To further investigate the role of M during viral growth, we used a two-hybrid system to screen for host factors that interact with the M protein. Here, NADH: ubiquinone oxidoreductase complex assembly factor 4 (Ndufaf4) was identified as an M-binding partner, and this interaction was confirmed by yeast cotransformation and GST pulldown assays. The globular domain of M was mapped and shown to be critical for the M–Ndufaf4 interaction. Two double mutations (E156A/H157A, D180A/E181A) in M impaired the M–Ndufaf4 interaction. Overexpression of Ndufaf4 inhibited VSV propagation, and knockdown of Ndufaf4 by short hairpin RNA (shRNA) markedly promoted VSV replication. Finally, we also demonstrate that the anti-VSV effect of Ndufaf4 is independent of activation of the type I IFN response. These results indicated that Ndufaf4 might exploit other mechanisms to affect VSV replication. In summary, we identify Ndufaf4 as a potential target for the inhibition of VSV propagation. These results provided further insight into the study of VSV pathogenesis.

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Acknowledgments

This work was supported by Taishan Scholar and Distinguished Experts (H.H.) (tspd20181207) and the National Nature Science Foundation of China (Nos. 31902257).

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Authors and Affiliations

  1. Ruminant Diseases Research Center, College of Life Sciences, Shandong Normal University, 88 East of Wen-hua Road, Jinan, 250014, Shandong, PR China

    Wei Pan, Zhihao Shen, Hongmei Wang & Hongbing He

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  1. Wei Pan
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  2. Zhihao Shen
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  3. Hongmei Wang
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  4. Hongbing He
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Contributions

WP and HH conceived and designed the study. WP and ZS performed the experiments. HW wrote the manuscript. All authors read and approved the final version of the manuscript.

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Correspondence to Hongbing He.

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Edited by Zhen F. Fu.

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Pan, W., Shen, Z., Wang, H. et al. The host cellular protein Ndufaf4 interacts with the vesicular stomatitis virus M protein and affects viral propagation. Virus Genes 57, 250–257 (2021). https://doi.org/10.1007/s11262-021-01833-0

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  • DOI: https://doi.org/10.1007/s11262-021-01833-0

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