Tuesday, November 19, 2013

Refreshed post: virus replication, dynamic modeling and within-host competition

My motivation for this post came from a great course I took, Ecology of Infectious Diseases. (In addition I am trying to not to be a sluggard!) The theme of the course is: imagine you are a microparasite (pathogen) that is willing to take every chance to survive. This leads my interesting thoughts on a paper by B R. Levin et al. In the section titled "Within-Host Population Dynamics of Pathogen Proliferation", he wrote: 

If the course of a microparasite infection in a vertebrate host were described without jargon, the process would be readily recognized as one of population dynamics and evolution. 

This perspective on pathogenesis and the immune response as ecological, population-dynamical, and evolutionary processes has been well recognized for some time (11). However, it has had little impact on contemporary research on the mechanisms of pathogenesis. Much of this research is qualitative rather than quantitative, and it can be described as a quest to characterize (genetically, biochemically, and physiologically) the interaction between infectious pathogens and the host's immune defenses. Although this research provides an indispensable basis for understanding pathogenesis and the host's response to infection, it tells only a part of the story. A complete account of the course of an infectious disease must include a quantitative description of the major forces that determine the abundance, diversity, and distribution of a pathogen population within an infected host and the immune defenses involved in its control.   

It is fascinating that the author pointed out the same thing came to me when I learned human population genetics. Why wouldn't we study viruses from a population biology point of view?

For decades the virologists characterized function of tremendous amount of viral proteins, host factors interaction, by saying that "XXX protein interacts with XXX host factors, which is increased/decreased during infection". These facts are important but only "parts of the story". For some reasons would trust the author as we always lose a global view in biomedical research. 

Viruses could be great source to study from population genetics of view, if we think the genome of every virus as the haplotype of every individuals. Some alleles in the viral genome confers "susceptibility" to the host, that is, loss of pathogenicity/infectiousness. This sounds very familiar when an allele in human was found causative of the susceptibility to a pathogen in a human subpopulation. 

Another way to think about the viral population genetics is to refer the mosaicism of the organism. The viruses with slightly different genome function as a whole parasite. These minute mutations of each viral particle have a huge impact on the population level. This sounds like the quasi species theory proposed long time ago.

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