**2.4. Viruses target mitochondrial DNA and disable host cells**

Numerous viruses appear to have adopted a "strategy" of damaging the host cell mitochondrial DNA to control the whole cell. For example, the herpes simplex virus (HSV) causes productive and latent infections in human hosts by disruption of mitochondrial function. The HSV-1UL12 gene encodes two distinct yet similar proteins, UL12 and UL12.5. UL12 is an alkaline nuclease, and UL12.5 is an N terminally truncated 500-aa polypeptide that lacks the first 126 residues of UL12. UL12 plays a crucial role in viral genome replication and processing; UL12.5 also has nuclease and strand-exchange activities but does not accumulate in the host cell nucleus. Instead, UL12.5 localizes predominantly to the mitochondria, where it triggers massive degradation of mitochondrial DNA during early HSV replication. In particular, UL12.5 occurs directly within the mitochondrial matrix, and its nuclease activity degrades mtDNA [43]. HIV and hepatitis C virus infections cause metabolic stress due to mtDNA depletion in coinfected patients [44]. The Zta protein encoded by Ebola virus (EBV) genome translocates into mitochondria and interacts with mitochondrial single-strand protein, which ultimately affects mtDNA replication [45]. The OS generated during HCV infection also interferes with mtDNA [31].
