Monday, February 14, 2011

Measles, Influenza (A), and adenosine deaminase

Figure 2

Measles and Influenza are both negative sense, single-stranded, helical, envelope-encased RNA viruses.  Both viruses depend on their own RNA dependant RNA polymerases to replicate.  Unlike DNA polymerase machinery, RNA polymerase does not proofread; instead, viral replication utilizing RNA polymerase facilitates rapid mutation.  RNA viruses, particularly influenza, take advantage of this facet of their replication, evading eradication by the immune system by mutating into different strains.

In some cases, however, mutations can lead to inactivated strain of the virus.  Though there are many mechanisms by which host cells restrict viral replication, one very common mechanism is the release of interferons (IFNs).  These IFNs induce the activation of cytidine and adenosine deaminases (enzymes that break down nucleic acids).  One adenosine deaminase that acts upon RNA was investigated recently because of its “demonstrable enzymatic activity.”  Though some viral infections have been shown to utilize ADAR editing to their advantage, generally ADAR-edited RNA viral genomes are limited to the population of negative-stranded viruses such as the influenza virus are tend to lose functionality.  Recently, a further investigation was performed in order to analyze the live attenuated pediatric measles-mumps-rubella virus (MMR) and the seasonal influenza virus vaccines and their interactions with ADAR-1. In the case of the influenza virus, it was found that ADAR-1 caused hypermutations that stemmed from changing As to Gs.  What has yet to be studied, are the effects of these mutations: Are the hypermutated viruses potentially functional and dangerous? Or do these mutations contribute to the attenuation seen in vaccines? Though a lot more research is necessary to understand the ADAR-1 and hypermutation, this concept of hypermutation as a limitation of virulence is a incredibly interesting finding that could lead to new treatments and preventions for viral infections.


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