One virus particle can be enough to cause infection
In the vast majority of systems, it is unknown how many individual pathogens are required to cause infection of a host organism. Estimates of this number are necessary to predict the likelihood that hosts are infected by multiple genotypes, and so predict the magnitude of genetic drift, the evolution of new pathogen genotypes and the interactions between pathogens and their hosts – all features which are highly relevant in the face of an influenza pandemic. These interactions include competition, complementation and recombination. There is experimental evidence that the number of virions causing an infection can be small, as shown by the data from two experimental approaches. First, genetic drift can be very strong when low virus doses are used, suggesting that only a small number of virions caused the infection. Second, results of dose–response experiments suggest that the number of virions causing infection is in some instances very small. Although the data suggest that the number may be small, there has been no absolute proof that one virus particle is enough be enough to cause infection of a host. Recent research with insect viruses has now shown that one virus particle is enough to cause infection and subsequent disease.
Virus populations are usually composed of collections of variants. In order to investigate whether virus particles (virions) can cause an infection independently from each other, and therefore individually, the researchers set up an experiment with two marked virus variants. The results showed that exposure to a low dose of virus particles resulted in a small number host infections, around 20%. The majority of these hosts turned out to be infected by a single virus genotype. In contrast, exposure to a high dose of virus resulted in virtually all the hosts becoming infected. Here most of the hosts were infected by both types of virus and only 14% were infected by only one of the variants.
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Based on the assumption that every virus particle operates independently from all other virus particles, the researchers set up a probability model to predict how many virus particles have caused an infection and how many different virus genotypes are present in infected hosts. The results of the infection experiments show that virus particles can indeed act independently, and that a single virus particle can be enough to cause an infection.
In infection caused by few virus particles (as may occur frequently in natural situations), the number of virus particles determines the degree of virus diversity that will be present within the host. This is an important finding because the interactions between virus variants, such as competition and exchanging genetic information, determine the progression of disease and the evolution of the virus. This is highly significant in the case of the new H1N1 influenza strain which has just entered the human population. Although each of the eight gene segments in the new virus has been seen in pigs in the past 10 years, this virus has only been in humans for a few months, and is quite unstable. Although less pathogenic than H5N1 influenza, which now seems to be endemic in countries like China, Indonesia, Vietnam and Egypt, recombination resulting in a virus which combines the high transmissibility of H1N1 with the killing power of the H5N1 becomes more likely as both viruses circulate in human populations.
Hold on tight, it might be a bumpy ride.
An experimental test of the independent action hypothesis in virus–insect pathosystems. 2009 Proc. R. Soc. B 276: 2233-2242
The independent action hypothesis (IAH) states that each pathogen individual has a non-zero probability of causing host death and that pathogen individuals act independently. IAH has not been rigorously tested. In this paper, we (i) develop a probabilistic framework for testing IAH and (ii) demonstrate that, in two out of the six virus–insect pathosystems tested, IAH is supported by the data. We first show that IAH inextricably links host survivorship to the number of infecting pathogen individuals, and develop a model to predict the frequency of single- and dual-genotype infections when a host is challenged with a mixture of two genotypes. Model predictions were tested using genetically marked, near-identical baculovirus genotypes, and insect larvae from three host species differing in susceptibility. Observations in early-instar larvae of two susceptible host species support IAH, but observations in late-instar larvae of susceptible host species and larvae of a less susceptible host species were not in agreement with IAH. Hence the model is experimentally supported only in pathosystems in which the host is highly susceptible. We provide, to our knowledge, the first qualitative experimental evidence that, in such pathosystems, the action of a single virion is sufficient to cause disease.
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Tags: Biology, infection, Influenza, insect, Medicine, Microbiology, Science, Virology, virus


