Caspase-Dependent Apoptosis Induction via Viral Protein ORF4 of Porcine Circovirus 2 Binding to Mitochondrial Adenine Nucleotide Translocase 3

Journal of Virology
Cui LinJiyong Zhou

Abstract

Apoptosis is an essential strategy of host defense responses and is used by viruses to maintain their life cycles. However, the apoptotic signals involved in virus replication are poorly known. In the present study, we report the molecular mechanism of apoptotic induction by the viral protein ORF4, a newly identified viral protein of porcine circovirus type 2 (PCV2). Apoptosis detection revealed not only that the activity of caspase-3 and -9 is increased in PCV2-infected and ORF4-transfected cells but also that cytochrome c release from the mitochondria to the cytosol is upregulated. Subsequently, ORF4 protein colocalization with adenine nucleotide translocase 3 (ANT3) was observed using structured illumination microscopy. Moreover, coimmunoprecipitation and pulldown analyses confirmed that the ORF4 protein interacts directly with mitochondrial ANT3 (mtANT3). Binding domain analysis further confirmed that N-terminal residues 1 to 30 of the ORF4 protein, comprising a mitochondrial targeting signal, are essential for the interaction with ANT3. Knockdown of ANT3 markedly inhibited the apoptotic induction of both ORF4 protein and PCV2, indicating that ANT3 plays an important role in ORF4 protein-induced apoptosis during PCV2 infect...Continue Reading

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Citations

Oct 12, 2018·Transboundary and Emerging Diseases·Huijuan WangJiyong Zhou
Jul 26, 2019·Journal of Virology·Huijuan WangJiyong Zhou
Jun 26, 2020·Frontiers in Microbiology·Jianwei ZhouJiyong Zhou
Jan 12, 2019·Frontiers in Veterinary Science·Francini KlaumannJoaquim Segalés
Sep 20, 2020·BMC Veterinary Research·Yinlan XuNa Sun
Sep 21, 2018·Frontiers in Microbiology·Yuhong PanAnchun Cheng
Feb 20, 2021·Frontiers in Cellular and Infection Microbiology·Yanting ZhangRenyong Jia

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