Friday, July 1, 2016

Generalized Selection, Innate Immunity, and Viruses Conclusion

After conducting their research, the scientists discovered that culturing VSV in MDCK cells led to populations of generalists, meaning that the viral progeny can adapt to the host and evade the immune system of similar related hosts.  Generalists can adapt to different habitats and function accordingly in order to survive.  The specialist population, or the viral progeny from the HeLa-adapted populations of VSV, were believed to be less fit in unpredictable environments than the generalist populations since they did not experience selection and did not adapt to the innate immunity of the host.

One of the factors of host breadth, or the ability to adapt to hosts, is cell-surface proteins.  Proteins on the cell wall dictate what viruses can attach to the cell and what viruses cannot.  The viruses that can attach are the ones that can perform viral replication.  VSV, the virus used in the experiment, is not affected by the proteins on the cell wall, meaning that they will have no problem entering the host.  This means that the proteins on the cell wall will not affect the fitness of the virus, only the immune system can affect the virus.

The results of the experiment showed the scientists that the evolution and selection of a virus are key factors in determining the fitness of a viral population.  Understanding how the environment affects a virus can show how a virus can maintain beneficial host-antagonistic alleles, or alleles that code for a virus's virulence, including the ability to evade the innate immunity, or immune system, and infect the host.  A competent IFN environment--an immunocompetent host with active interferons that activate the immune system and protect the host cells--influences VSV to maintain the beneficial alleles to survive and successfully replicate in the host.  However, a relaxed IFN environment, or an immunodeficient host, leads to the loss of the host-antagonistic alleles.

The viral progeny from the alternate-host populations lived half of its evolutionary life in the MDCK host.  However, the viral progeny did not efficiently adapt and maintain the alleles needed to evade the innate immunity because the VSV was not under the selective pressure long enough.  The VSV was cultured in differing environments, leading scientists to believe that the adaptation to multiple environments influenced the maintenance and expression of beneficial alleles, and ultimately generalization.  Despite this, the viral progeny did not have high fitness and did not survive as well as hoped in the immunocompetent novel hosts (PC-3 Cells).  The novel hosts were used as test sites to determine the fitness of the VSV.  The researchers believed that the maintenance of the host-antagonistic alleles led to the loss of alleles that would express for the growth of the VSV in 3 of the 4 alternate-host populations.

The scientists also concluded that only the innate immunity affects viral evolution, not the properties of the host.  They tested this with the VERO cells, or primate cells.  Scientists grew the generalist viral populations in MDCK cells, or canine kidney cells, and discovered that they also had high fitness in the VERO cells since the MDCK-evolved populations were able to evade the innate immunity of the VERO cells due to robust viral selection.

With their research, the scientists ultimately concluded that the innate immunity of a host impacts the evolution of a virus.


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