Increased ATP generation in the host cell is required for efficient vaccinia virus production

• Published in: Journal of biomedical science Vol. 16; no. 1; p. 80
• Main Authors: Chang, Chia-Wei, Li, Hui-Chun, Hsu, Che-Fang, Chang, Chiao-Yen, Lo, Shih-Yen
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 02.09.2009; BioMed Central; BMC
• Subjects: Adenosine Triphosphate - biosynthesis; Adenosine Triphosphate - physiology; Apigenin - pharmacology; Cytarabine - pharmacology; DNA; DNA replication; Electron transport; Electron Transport - drug effects; Electron Transport Complex IV - biosynthesis; Electron Transport Complex IV - genetics; Gene Expression Profiling; Gene Expression Regulation, Viral; Health aspects; HeLa Cells - virology; Host-Pathogen Interactions; Humans; Infection; Messenger RNA; NADH Dehydrogenase - biosynthesis; NADH Dehydrogenase - genetics; Oligomycins - pharmacology; Proto-Oncogene Proteins c-bcl-2 - physiology; Reverse Transcriptase Polymerase Chain Reaction; RNA, Small Interfering - pharmacology; Second Messenger Systems - physiology; Up-Regulation; Vaccinia; Vaccinia virus - physiology; Viral Plaque Assay; Viral proteins; Viral Proteins - genetics; Viral Proteins - physiology; Virus Replication - physiology
• ISSN: 1423-0127; 1021-7770; 1423-0127
• DOI: 10.1186/1423-0127-16-80

To search for cellular genes up-regulated by vaccinia virus (VV) infection, differential display-reverse transcription-polymerase chain reaction (ddRT-PCR) assays were used to examine the expression of mRNAs from mock-infected and VV-infected HeLa cells. Two mitochondrial genes for proteins that are part of the electron transport chain that generates ATP, ND4 and CO II , were up-regulated after VV infection. Up-regulation of ND4 level by VV infection was confirmed by Western blotting analysis. Up-regulation of ND4 was reduced by the MAPK inhibitor, apigenin, which has been demonstrated elsewhere to inhibit VV replication. The induction of ND4 expression occurred after viral DNA replication since ara C, an inhibitor of poxviral DNA replication, could block this induction. ATP production was increased in the host cells after VV infection. Moreover, 4.5 μM oligomycin, an inhibitor of ATP production, reduced the ATP level 13 hr after virus infection to that of mock-infected cells and inhibited viral protein expression and virus production, suggesting that increased ATP production is required for efficient VV production. Our results further suggest that induction of ND4 expression is through a Bcl-2 independent pathway.