Wednesday, 28 January 2015

Mitochondrial dynamics and viral infections: A close nexus



Mohsin Khan, Gulam Hussain Syed, Seong-Jun Kim and Aleem Siddiqui

This paper discusses how viruses manipulate cellular machinery, in particular mitochondria, for their own good. It makes sense for viruses to target mitochondria because it gives them control over the energy production of the cell: the more energy, the more viruses can be made. Perhaps more importantly, by targeting mitochondria the virus may have some control over the survival of the cell as mitochondria are involved in apoptosis. The virus wants to keep the cell alive for as long as possible in order to produce many copies of itself before bursting out the cell and killing it. The paper focusses on how viruses influence mitochondrial dynamics, and how this may influence cell survival. Several viruses and their effects on mitochondrial dynamics are discussed.


Hepatitus C viruses (HCV) cause ER stress, release of calcium from the ER and subsequent uptake of calcium by mitochondria which then depolarize and become dysfunctional. Proteins of HCV can associate directly with the mitochondria and localize to the outer mitochondria membrane, or the mitochondria-associated-ER membrane (MAM). Once associated with MAM, HCV proteases are able to cleave mitochondria associated antiviral signalling proteins (MAVS). MAVS play an important role in immune signalling, and by cleaving MAVS, the virus may be able to evade an immune response. Other HCV proteins are able to perturb the activity of complex I of the respiratory chain, promote mitochondrial calcium uptake and promote ROS production. The virus also messes with mitochondrial quality control, by altering Drp-1 phosphorylation which causes mitochondria to fragment, and increasing the expression of Parkin and PINK1 which promotes mitophagy. When Parkin and Drp1 were depleted from HCV-infected cells, the virus could not induce fragmentation and mitophagy any more, but suddenly apoptotic signalling and cytochrome c release increased, with apoptosis as a consequence. It may thus be that the HCV induced fission followed by mitophagy boosts mitochondrial quality control and helps to prevent cytochrome c release, so that the cell survives longer.

Besides hepatitus C, they also discuss the hepatitus B virus, the Epstein–Barr virus, Human cytomegalovirus, Pseudorabies virus, Influenza virus, Measles virus, Newcastle disease virus, and the SARS coronavirus. Most of these virusses trigger mitochondrial fission, except for the SARS coronavirus, which causes mitochondria to fuse. Why does this virus work differently? Read the paper, and perhaps the answer will be there..

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