Evolutionary Arms Race Between Virus and Host

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Vaccines are the agents that give us protection from infectious agents upon introduction into our body. Several vaccines have been successfully used against various infectious pathogens and have thus substantially increased human life-span. However, have you ever thought why vaccines against several pathogens such as Human immunodeficiency virus (HIV) and Hepatitis C Virus (HCV) are not developed yet? Why do HCV patients develop resistance against antiviral drugs? Or why do people repeatedly get flu? The answers lie in a natural process called continuous evolution of the infectious organisms. Viruses are some of the smallest organisms found in the universe and are considered as connecting link between living and non-living world. This is because they can not replicate (make more of the same virus particles) outside a suitable host organism, but gain life inside them. They infect plants, animals, humans and even amoeba and bacteria. Viruses evolved millions years ago either from complex molecules of protein and nucleic acid (DNA or RNA) before appearance of cell on earth, or from escaped nucleic acid from the genes of a larger organism.

What makes virus such unparalleled successful infectious organisms? For a virus, the host body is its universe and each infected cell is the playground. Host immune system and antiviral drugs enforce a selection pressure on the replicating virus population. Inside the body the virus keeps reproducing rapidly with high mutation rate (particularly in RNA virus). Mutations are referred to as the errors generated in the genetic material of an organism and that in turn  cause changes in the amino acid sequences of the corresponding decoded proteins. Generation of these mutations is a deliberate strategy for diversity in order to produce large number of variants on which the selection pressure (the pressure exerted by the environment on the organism, in this case virus) acts. Out of the many variants, some may achieve the drug resistance and some others may gain higher infectivity. These smarter variants become the major population in due course of time and emerge as “better fit” (evolved) virus in comparison to the parental virus. The other unfit populations get eliminated. Such ongoing changes keep accumulating in every generation and give rise to new viral strains. In this sense, viral evolution follows the Darwinian laws of evolution.

The high mutation rate of HIV is the reason why an effective HIV vaccine is still not developed against it.  Similar mutations also help viruses to develop resistance against drugs. Recently, an HCV mutant was found in patients which was resistant to the sofosbuvir, the most effective drug that was introduced  into the market only a few years ago

(1). Such mutants, products of high viral mutation and continuous selection through generations, pose great challenge to the current HCV therapy. Influenza virus evolves even at higher rates through a mechanism known as antigenic shift. Influenza infects birds and mammals. Genome of Influenza virus consists of eight RNA segments, each carrying certain genes. Different influenza virus strains which infect different species can exchange genes via antigenic shift.  In 1957 the pandemic caused by H2N2 virus was a result of re-assortment between human H1N1 and avian influenza A strains

(2). In 2009 swine flu which caused thousands of death worldwide was a triple re-assorted flu virus of bird, swine and human

(3). Alongside the virus, its host also keeps evolving, albeit at much slower rate. Virus may have posed a selection pressure for the host immune system during its evolutionary history. Either the surviving viral populations continued to produce their resistant offspring (Darwinism) or a subset of host population with lower inflammatory (antiviral) response passed the pathogens through generations (Lamarckism). Host cells have mechanisms for correcting the mistakes incorporated in nucleic acid during replication to check the mutations from being passed on to offspring. However, evolution in the higher order host is a longer process since it is limited to rearrangement of genetic material during sexual reproduction. Life cycle of a virus is just few hours and viral replication generates millions of new viral particles. On the other hand, a human requires about 20 years for reproductive maturity and gives birth to a few children. This limits the visibility of evolution of host in contrast to the viruses. Interestingly, genomes of most vertebrate species contain thousands of ancient retroviruses (a class of virus whose genome integrates into that of the host; e.g. HIV) derived sequences. Approximately 5-8% of Human genome is made up of retroviruses 

(4). These sequences now function as transcriptional elements on human genes. Proteins derived from these sequences have shown to serve important host functions such as reproduction and development. Bats show the evolutionary loss of immune response specific genes. This may be the reason why bats are reservoirs for several human pathogens. However whether the evolution of bat immune system followed Darwinism or Lamarckism is yet to be explored. Simian immunodeficiency virus (SIV) has infected monkeys millennia ago and this virus is unable to put a health hazard in them at present era whereas HIV which is recently identified in humans and evolutionarily related to SIV is a potent killer of humans. Researchers recently found that a mutation in cell surface receptor, required for HIV binding to its host cell, makes a small set of human resistant to HIV

(5). The population which shows the mutation in cell surface receptor will show a survival advantage if HIV causes a pandemic in future.  In this way virus can give evolutionary advantage to a subset of population for successful survival. Co-evolution of human and virus is visible by regional variations in genotype prevalence.

Evolution of virus and host goes on hand in hand. This is a co-evolutionary arms race which occurs concurrently in both virus and its host. The weapon of host is its diverse immune system whereas virus believes on its population and mutability. Because of this battle, both the host as well as the virus not only keep evolving themselves but also define a direction for evolution of their opposition.

Suggested reads:

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<!--[if !supportLists]-->2-    <!--[endif]-->Scholtissek C, et al (1995) Molecular evolution of influenza viruses. Virus Genes. 11(2–3): 209–215.

<!--[if !supportLists]-->3-    <!--[endif]-->Vladimir T, et al (2009) Geographic Dependence, Surveillance, and Origins of the 2009 Influenza A (H1N1) Virus. New England Journal of Medicine. 361 (2): 115–119. 

<!--[if !supportLists]-->4-    <!--[endif]-->Belshaw R, et al (2004) Long-term reinfection of the human genome by endogenous retroviruses. Proc Natl Acad Sci U S A. 101(14): 4894–4899

<!--[if !supportLists]-->5-    <!--[endif]-->Dean M, et al (1996) Genetic restriction of HIV-1 infection and progression to AIDS by a deletion allele of the CKR5 structural gene. Hemophilia Growth and Development Study, Multicenter AIDS Cohort Study, Multicenter Hemophilia Cohort Study, San Francisco City Cohort, ALIVE Study. Science 273: 1856–1862.

 

Article by:

Manish Kumar Johri, SRF

New R&D building,

CSIR-Centre for Cellular and Molecular Biology

Uppal Road, Hyderabad-500007.

Email: manijohri@gmail.com

Posted By : ScienceIndia Administrator