Do viruses evolve to protect their hosts?
It is sometimes said that viruses evolve to become less pathogenic to their hosts so that they do not kill them in order to allow themselves to replicate. This is said, but is it true?
For some time, Esteban Domingo and his co-workers in Madrid have worked on genetic variation in viruses, particularly with respect to foot and mouth disease virus (FMDV). One of their particular interests has been in virus quasispecies, the complex and dynamic mixture of genetic variants which occurs when viruses, particular RNA viruses, propagate their genomes (Viruses as quasispecies: biological implications. 2006 Curr Top Microbiol Immunol. 299: 51-82).
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Mutation rates at individual positions in a virus genome are affected by the nucleotide sequence of the template as well as by environmental factors, but the evolution of virus quasispecies is also dependent on the population size of the virus. Repeated genetic bottlenecks lead to fitness losses and viruses with mutations which affect their replication. In contrast, large virus populations may result in fitness gains. However, there’s no such thing as a free lunch, and fitness gains in one environment often lead to fitness losses in an alternative situation. Viruses occupy only a tiny portion of their potential “sequence space”, i.e. their total possible genetic variation. This shows that there is a limited tolerance to mutations and may open new avenues for fighting virus infections. Virus mutants are continuously generated during RNA genome replication, and they are not devoid of biological relevance. The evidence indicates that the presence of virus quasispecies contributes to viral pathogenesis, modulates the expression of phenotypic traits, may include memory genomes that reflect the past evolutionary history of the virus, and can participate in virus extinctions.
Recently, Domingo and his colleagues have investigated the role of virus quasispecies in replication fitness and cell killing capacity (Molecular Basis for a Lack of Correlation between Viral Fitness and Cell Killing Capacity. PLoS Pathogens Vol. 3, No. 4, e53). Virulence is a measure of the degree of harm that parasites inflict upon their hosts. It is generally accepted that one of the components of a parasite’s virulence is fitness, the capacity of the parasite to multiply in the host. In their recent study, the authors used FMDV to show that virulence and fitness – measured in the same biological environment provided by cells in culture – can be unrelated traits. Mutations in the virus genome decreased fitness dramatically, but not necessarily virulence. By constructing chimeric mutant viruses, they were able to show that virulence is influenced by only some of the FMDV genes, while fitness is influenced by the entire genome. For this reason, virulence is more robust (resistant to mutations) than fitness. The fact that virulence can be unrelated to fitness has implications for the design of virus vaccines because it suggests that it is possible to design high fitness, low virulence strains to stimulate the host immune response. Furthermore, in modeling studies it cannot be assumed that virulence is equal to fitness.
These results remind me of work I was involved in many years ago looking at the reversion of the Sabin live attenuated poliovirus vaccines to virulence. Although oral poliovirus vaccine is very safe and induces very good immunity, there is a risk of around one in a million cases of a vaccinated healthy individual developing poliomyelitis. In these rare cases, we were able to show that a frighteningly small number of nucleotide changes, in very specific locations, was able to cause the attenuated vaccine strain to become as virulent and as capable of causing paralysis as any wild poliovirus (Increased neurovirulence associated with a single nucleotide change in a noncoding region of the Sabin type 3 poliovaccine genome. 1985 Nature 314: 548-550).
And yet oral poliovirus vaccine has brought us to the brink of eradicating poliovirus. We should not neglect the value of live attenuated virus vaccines – measles virus is next on the list for eradication after polio, brought to it’s knees by MMR vaccine. If only we had such safe and effective vaccines against dengue fever, Ebola virus and HIV.
why do viruses kill their hosts? Also, if the parvo virus kills a dog, and the dog is then put in a thick plstic bag and then buried, will the virus continue to live on for years, feeding off the host dog which is rotting in the ground?
One more question: If the parvo virus infected deceased dog is buried 2 feet underground, as required by law in FLorida, in a thick black plastic bag, can it be a threat, in the future(after the thick plastic bag disintegrates), to infecting well water, when there is a well about 100 feet away?
> why do viruses kill their hosts?
Most viruses don’t – why would they? The ones that do are “less good at being viruses” than the talented viruses. And sometimes, the host (which doesn’t want to die) also gets it wrong. C’est la vie. Or not.
> Also, if the parvovirus kills a dog, and the dog is then put in a thick plastic bag and then buried, will the virus continue to live on for years, feeding off the host dog which is rotting in the ground?
Nope. Viruses need living host cells.