phi-6 bacteriophageThe viruses I’m particularly interested in, herpesviruses and adenoviruses, tend to have a limited host range. For example, human cytomegalovirus doesn’t infect mice, and mouse cytomegalovirus doesn’t infect humans. Some of the reasons underlying these host specificities are starting to be mapped out at the molecular level (I’ve talked about a couple of examples here). A larger question, though, is why viruses become host-restricted in the first place. After all, a few viruses, such as rabies, are able to infect a huge range of species. Presumably it would benefit a virus to have a wider range of potential hosts available. Why haven’t more viruses evolved ways of infecting many species?

Part of the answer is presumably that it’s a hard enough task for a virus to infect a single host, and the more fine-tuned to one host a virus becomes, the less well-adapted to other hosts it is. We see this, perhaps, in influenza viruses; those that are adapted well to infecting birds are poorly adapted to infecting humans, at least partially because their receptors are better suited to binding molecules. (But let’s not lose track of the fact that avian influenza viruses are nevertheless capable of infecting many species of birds, making them much more versatile than cytomegaloviruses and their ilk.) But this is kind of a hand-waving answer, based on hunches and guesswork. I’d like to see a more formal test of the hypothesis.

A paper published in Evolution last fall1 takes a run at explaining host restriction. It’s far enough from my fields that I don’t want to critique it in great detail, but it makes some intriguing suggestions, some of which ring truer than others to me.

Apple maggot flyDuffy et al. argue that speciation and host adaptation are tightly linked. (That was what caught my attention, because for the most part you get a new herpesvirus when its host speciates; so you have a combination of reproductive isolation and tight host adaptation.) Speciation, at least in this context, means reproductive isolation. The way viruses become reproductively isolated is when they can’t infect the same host; so for viruses “reproductive isolation” is the same as “host restriction”. Duffy et al here are using host restriction as a model for ecological adaptation; one of the analogies they use is the famous apple maggot fly, which has developed reproductive isolation by breeding on fruit with different ripening times.

There’s some previous work on this in viruses; I wasn’t familiar with it, though, and the reviews2 are not easily accessible to me right now:

Previous experiments have shown that viral adaptation to a single host is often accompanied by a reduced ability to infect alternative hosts … For example, adaptation of the bacteriophage X174 to Salmonella enterica was accompanied by a reduced ability to infect Escherichia coli … One might logically conclude, therefore, that adaptation to a novel host–a host that is not infectible by the wild-type virus–should often produce an evolved virus that no longer infects the ancestral host, so that the host ranges of the closely related wild-type and evolved viruses no longer overlap.

(My emphasis.)

The model virus here is bacteriophage φ6. (I don’t know much about the phages, which is probably one reason I’ve missed out on the history of this work.) φ6 normally infects various Pseudomonas spp.For this work, they  started with a phage variant with a broad host specificity and used it to infect P. pseudoalcaligenes, which is not a normal host for the phage. They grew the phage for about 150 generations on this host, and then tested for host specificity, arguing that host specificity would not be directly selected, but (if it occurred) would have to be a side-effect of adapting to the host. That was indeed what they saw:

Thus, in all three populations showing reduced host range (increased host specificity), the phenomenon was caused indirectly by a single mutation that conferred a selective advantage on the novel host P. pseudoalcaligenes (increased host performance). … in φ6 assortative mating (host range) and ecological adaptation (performance on the novel host) had a shared genetic basis. … assortative mating evolved via a biologically simple “no-gene” mechanism in which assortative mating arises as a pleiotropic effect of mutations that produce ecological adaptation.

Vaccine-strain (MVA) vaccinia budding from chicken cells(My emphasis again)

I wonder what other aspects of a virus are involved. Are different kinds of virus (RNA vs. DNA, large vs. small, something else?) more or less likely to become host adapted/host restricted? This may seem like an academic question, but in fact I think it has a lot of clinical relevance. Apart from the question of emerging viruses and how they leap from one ecological niche (i.e. host) to a new one (i.e. us), there’s also a vaccine counterpart.

One of the traditional, and very effective, ways of developing a viral vaccine is to culture it on cells from an abnormal host — chicken cells, for example, for a human virus. In the process of adapting to the new host cells, the virus often loses virulence for the original host, and becomes a safe vaccine. I don’t know if there’s any kind of formal theory underlying this process or if it’s mostly empirical; this work may eventually lead to a more defined and rationale approach to developing safe vaccines that have less chance of reverting back to virulence in humans.


  1. Duffy, S., Burch, C.L., Turner, P.E. (2007). Evolution of Host Specificity Drives Reproductive Isolation Among RNA Viruses. Evolution, 61(11), 2614-2622. DOI: 10.1111/j.1558-5646.2007.00226.x []
  2. Ebert, D. 2000. Experimental evidence for rapid parasite adaptation and its consequences for the evolution of virulence. Pp. 163-184 in R. Poulin, S. Morand, and A. Skorping, eds. Evolutionary biology of host-parasite relationships: theory meets reality. Elsevier Science, Amsterdam.
    Fenner, F., and J. Cairns. 1959. Variation in virulence in relation to adaptation to new hosts. Pp. 225-249 in F. M. Burnet, and W. M. Stanley, eds. The viruses: biochemical, biological and biophysical properties. Academic Press, New York.[]