Cell death pathways and viruses: Role of microRNAs

Viral infections lead to the death of more than a million people each year around the world, both directly and indirectly. Vi-ruses interfere with many cell functions, particularly critical pathways for cell death, by affecting various intracellular medi-ators. MicroRNAs (miRNAs) are a major example of these me-diators because they are involved in many (if not most) cellular mechanisms. Virus-regulated miRNAs have been implicated in three cell death pathways, namely, apoptosis, autophagy, and anoikis. Several molecules (e.g., BECN1 and B cell lymphoma 2 [BCL2] family members) are involved in both apoptosis and autophagy, while activation of anoikis leads to cell death similar to apoptosis. These mechanistic similarities suggest that common regulators, including some miRNAs (e.g., miR-21 and miR-192), are involved in different cell death pathways. Because the balance between cell proliferation and cell death is pivotal to the homeostasis of the human body, miRNAs that regulate cell death pathways have drawn much attention from researchers. miR-21 is regulated by several viruses and can affect both apoptosis and anoikis via modulating various tar-gets, such as PDCD4, PTEN, interleukin (IL)-12, Maspin, and Fas-L. miR-34 can be downregulated by viral infection and has different effects on apoptosis, depending on the type of vi-rus and/or host cell. The present review summarizes the exist-ing knowledge on virus-regulated miRNAs involved in the modulation of cell death pathways. Understanding the mecha-nisms for virus-mediated regulation of cell death pathways could provide valuable information to improve the diagnosis and treatment of many viral diseases.

Automated summary

Viral infections can alter cell death pathways and affect the life and death of cells.