Editors' ChoiceInfluenza

Mixing it up

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Science Translational Medicine  24 Jun 2015:
Vol. 7, Issue 293, pp. 293ec104
DOI: 10.1126/scitranslmed.aac7159

The influenza A and B virus genomes comprise eight individual segments of RNA, each encoding one or two proteins essential for virus replication. When two different influenza viruses coinfect the same cell, a mixture of eight genome segments derived from both strains can be incorporated into a single progeny virus. Segment reassortment results in a unique constellation of viral genes that may, in a given host, provide a fitness advantage over viruses encoding either parental genome separately. Reassortment among genetically compatible human and animal influenza A virus segments is believed to be a prerequisite for pandemic influenza.

In the laboratory, genome reassortment is easily demonstrated, but the frequency with which reassortment occurs in nature is unknown. Numerous host, viral, and environmental variables can affect the efficiency of influenza virus transmission; thus, in nature, stochastic effects might limit the opportunities for productive host coinfection, and thus reassortment.

In a new study, Tao et al. simulated the “natural” spread of influenza viruses in guinea pigs. They infected donor guinea pigs with two genetically similar viruses and then looked for evidence of genome reassortment in guinea pigs that became infected by transmission from the donors. They used optimal transmission conditions to maximize the probability of coinfection in the exposed guinea pig. Even so, they hypothesized that reassortment frequency would be limited by the inherently stochastic nature of inter-host transmission.

Surprisingly, however, the authors found that the majority of exposed guinea pigs were productively coinfected by both viruses, whether they were exposed to a single donor guinea pig coinfected with both viruses or to two donors each infected with a different virus. In addition, in coinfected animals, significant segment reassortment was observed; typically, 50 to 100% of progeny viruses isolated from the exposed guinea pigs contained genome segments from both parental variants. Thus, reassortment does not seem to be particularly affected by stochastic effects associated with transmission, at least between genetically similar viruses in guinea pigs.

Because pandemic influenza is thought to derive from reassortment between relatively dissimilar strains, the subsequent fitness of a reassorted genome is a critical factor in whether the reassortment spreads worldwide. These results suggest that reassortment likely occurs readily in nature and is probably less limited by coinfection opportunities than by progeny fitness.

H. Tao et al., Influenza A virus co-infection through transmission can support high levels of reassortment. J. Virol. 10.1128/JVI.01162-15 (2015). [Full Text] [Abstract]

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