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The mitochondrial carrier homolog 2 is involved in down-regulation of influenza A virus replication

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Abstract

Background

The mitochondrial carrier homolog 2 (MTCH2) is a mitochondrial outer membrane protein regulating mitochondrial metabolism and functions in lipid homeostasis and apoptosis. Experimental data on the interaction of MTCH2 with viral proteins in virus-infected cells are very limited. Here, the interaction of MTCH2 with PA subunit of influenza A virus RdRp and its effects on viral replication was investigated.

Methods

The human MTCH2 protein was identified as the influenza A virus PA-related cellular factor with the Y2H assay. The interaction between GST.MTCH2 and PA protein co-expressed in transfected HEK293 cells was evaluated by GST-pull down. The effect of MTCH2 on virus replication was determined by quantification of viral transcript and/or viral proteins in the cells transfected with MTCH2-encoding plasmid or MTCH2-siRNA. An interaction model of MTCH2 and PA was predicted with protein modeling/docking algorithms.

Results

It was observed that PA and GST.MTCH2 proteins expressed in HEK293 cells were co-precipitated by glutathione-agarose beads. The influenza A virus replication was stimulated in HeLa cells whose MTCH2 expression was suppressed with specific siRNA, whereas the increase of MTCH2 in transiently transfected HEK293 cells inhibited viral RdRp activity. The results of a Y2H assay and protein-protein docking analysis suggested that the amino terminal part of the viral PA (nPA) can bind to the cytoplasmic domain comprising amino acid residues 253 to 282 of the MTCH2.

Conclusion

It is suggested that the host mitochondrial MTCH2 protein is probably involved in the interaction with the viral polymerase protein PA to cause negative regulatory effect on influenza A virus replication in infected cells.

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Data availability

The datasets used during the present study are available from the corresponding author uponreasonable request.

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Funding

This work was supported by a grant from the Scientific and Technological Research Council of Turkey (TÜBİTAK; grant no: SBAG-112S518).

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Authors and Affiliations

  1. Institute of Health Sciences, Marmara University, Istanbul, Turkey

    Pınar Ulupinar

  2. University of Health Sciences, Kartal Koşuyolu High Speciality Educational and Research Hospital, Istanbul, Turkey

    Elif Çağlayan

  3. Department of Basic Pharmaceutical Sciences, Faculty of Pharmacy, Marmara University, Istanbul, Turkey

    Erkan Rayaman & Kadir Turan

  4. Department of Infection Biology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan

    Kyosuke Nagata

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  1. Pınar Ulupinar
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  2. Elif Çağlayan
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  3. Erkan Rayaman
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  4. Kyosuke Nagata
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Contributions

P.U., E.Ç., E.R. and K.T. conducted the experiments. P.U., E.Ç. and K.T. drafted the manuscript. K.N. and K.T. contributed to the conception and design of the study. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Kadir Turan.

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Ulupinar, P., Çağlayan, E., Rayaman, E. et al. The mitochondrial carrier homolog 2 is involved in down-regulation of influenza A virus replication. Mol Biol Rep 51, 642 (2024). https://doi.org/10.1007/s11033-024-09584-5

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