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Home / Equine Research Bank / Virus Genes / The host cellular protein Ndufaf4 interacts with the vesicul...
Virus genes2021; 57(3); 250-257; doi: 10.1007/s11262-021-01833-0

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

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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Publication Date: 2021-02-26 PubMed ID: 33635491DOI: 10.1007/s11262-021-01833-0Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research investigates how the interaction between a host cellular protein, Ndufaf4, and the matrix protein (M) of Vesicular stomatitis virus (VSV) affects the propagation of the virus. The authors identified that Ndufaf4 is a potential target for inhibiting the spread of VSV.

Research Methodology and Findings

  • The researchers used a two-hybrid system, a molecular biology technique used to discover protein-protein interactions, to identify proteins that interact with the VSV M protein.
  • NADH: ubiquinone oxidoreductase complex assembly factor 4 (Ndufaf4), a host cellular protein, was identified as an M-binding partner. This interaction was then confirmed through further testing using yeast cotransformation and GST pulldown assays.
  • The researchers found that the globular domain of the M protein was critical for the M-Ndufaf4 interaction. They also identified two double mutations inside the M protein that hindered the interaction.
  • The study investigated the effect of the Ndufaf4 on VSV propagation. It was found that overexpression of Ndufaf4 inhibited VSV propagation while reducing Ndufaf4 (by short hairpin RNA, shRNA) markedly promoted VSV replication.
  • Finally, through their research, the team confirmed that the effect of Ndufaf4 on VSV propagation was not reliant on the activation of type I IFN response. This suggests that Ndufaf4 likely uses other mechanisms to impact VSV replication.

Implications and Conclusion

  • The study shows how Ndufaf4 might be exploited to hinder VSV propagation. By understanding and manipulating this protein’s interactions with the M protein, it may be possible to prevent or slow down the spread of VSV.
  • This research provides further insight into the pathogenesis of VSV, a disease-causing virus in livestock. It can pave the way for the development of effective treatments or prevention strategies against the disease.
  • The authors conclude by identifying Ndufaf4 as a potential target for inhibiting VSV propagation. This suggests the value of future research into more precisely defining the mechanisms at play and leveraging them for therapeutic interventions.

Cite This Article

APA
Pan W, Shen Z, Wang H, He H. (2021). The host cellular protein Ndufaf4 interacts with the vesicular stomatitis virus M protein and affects viral propagation. Virus Genes, 57(3), 250-257. https://doi.org/10.1007/s11262-021-01833-0

Publication

Virus genes
ISSN: 1572-994X
NlmUniqueID: 8803967
Country: United States
Language: English
Volume: 57
Issue: 3
Pages: 250-257

Researcher Affiliations

Pan, Wei
  • Ruminant Diseases Research Center, College of Life Sciences, Shandong Normal University, 88 East of Wen-hua Road, Jinan, 250014, Shandong, PR China.
Shen, Zhihao
  • Ruminant Diseases Research Center, College of Life Sciences, Shandong Normal University, 88 East of Wen-hua Road, Jinan, 250014, Shandong, PR China.
Wang, Hongmei
  • Ruminant Diseases Research Center, College of Life Sciences, Shandong Normal University, 88 East of Wen-hua Road, Jinan, 250014, Shandong, PR China.
He, Hongbing
  • Ruminant Diseases Research Center, College of Life Sciences, Shandong Normal University, 88 East of Wen-hua Road, Jinan, 250014, Shandong, PR China. hongbinhe@sdnu.edu.cn.

MeSH Terms

  • Animals
  • Calmodulin-Binding Proteins / genetics
  • Cattle
  • Horses / virology
  • Host-Pathogen Interactions / genetics
  • Humans
  • Mutation / genetics
  • Swine / virology
  • Vesicular Stomatitis / genetics
  • Vesicular Stomatitis / virology
  • Viral Matrix Proteins / genetics
  • Virus Replication / genetics

Grant Funding

  • tspd20181207 / Taishan Scholar and Distinguished Experts (H.H.)
  • 31902257 / National Natural Science Foundation of China

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Citations

This article has been cited 3 times.
  1. Spedicati B, Pecori A, Concas MP, Santin A, Ruberto R, Nardone GG, D'Alessandro A, Tirelli G, Boscolo-Rizzo P, Girotto G. Scent of COVID-19: Whole-Genome Sequencing Analysis Reveals the Role of ACE2, IFI44, and NDUFAF4 in Long-Lasting Olfactory Dysfunction. Life (Basel) 2025 Jan 5;15(1).
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  2. Larrieux A, Sanjuán R. Murine colon cancer derived cells exhibit heterogeneous resistance profiles against an oncolytic virus. Sci Rep 2024 Nov 8;14(1):27209.
    doi: 10.1038/s41598-024-78313-6pubmed: 39516525google scholar: lookup
  3. Meng X-Y, Jiang Q-Q, Yu X-D, Zhang Q-Y, Ke F. Eukaryotic translation elongation factor 1 alpha (eEF1A) inhibits Siniperca chuatsi rhabdovirus (SCRV) infection through two distinct mechanisms. J Virol 2023 Nov 30;97(11):e0122623.
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