The World Killer – The Reasortment Risk is Real

One of my worst nightmares is a virus that is both highly lethal and highly contagious. The most likely candidate for such a virus is influenza, imo. Because it can spread efficiently while its host is still mobile, there is no evolutionary constraint on the development of a highly lethal strain. This is not true of Ebola or its relatives which incapacitate their victims before the viruses are ready to spread.

How likely is “the world killer” flu virus? Many flu viruses that spread efficiently among humans (seasonal and pandemic H1N1) already exist. One flu virus with a kill rate of over 70% also already exists – H5N1. A host can be infected with two flu viruses at the same time. These viruses can exchange genetic material to create a new, hybrid virus. This process is called reassortment.

Limited laboratory tests of whether H5N1 could combine with other flu viruses to create a highly lethal, highly infectious hybrid did not produce such a virus. However, a new report, based on a much more systematic effort, has.

From Li et al. (2010)

To evaluate the pathogenic potential of reassortant viruses between currently cocirculating avian H5N1 and human H3N2 influenza viruses, we generated all the 254 combinations of reassortant viruses between A/chicken/South Kalimantan/UT6028/06 (SK06, H5N1) and A/Tokyo/Ut-Sk-1/07 (Tok07, H3N2) influenza viruses by reverse genetics. We found that the presence of Tok07 PB2 protein in the ribonucleoprotein (RNP) complex allowed efficient viral RNA transcription in a minigenome assay and that RNP activity played an essential role in the viability and replicative ability of the reassortant viruses. When the pathogenicity of 75 reassortant H5 viruses was tested in mice, 22 were more pathogenic than the parental SK06 virus, and three were extremely virulent.

Virulence in this study was measure by the least amount of virus that could be given the mice and still kill 50% of them. Virus is measured in terms of plaque forming units (pfus). When I first read how little virus was necessary to kill the mice, I did a double-take:

… r1, r1,2 and r1,2,8 killed mice with ≤10 pfu.

That is very little indeed and suggests an extremely lethal virus, more lethal, in fact, than the parent H5N1 virus.

Based on another assay, the authors suggest that

…the introduction of the human PB2 segment into a reassortant virus could confer efficient growth at the lower temperature of the upper respiratory tract of humans, an ability that is critical for efficient transmission of pandemic viruses among humans.

The idea of a influenza virus that kills nearly all its victims and spreads with a cough is no longer science fiction. It could be born at any time. Its parents already exist.

Li, C., Hatta, M. Nidom, C. A., Muramoto, Y., Watanabe, S., Neumann, G. and Kawaoka, Y. (2010) Reassortment between avian H5N1 and human H3N2 influenza viruses creates hybrid viruses with substantial virulence. Proceedings of the National Academy of Science.

Related blogs
The polymerase basic protein 2 (PB2) gene of pandemic H1N1
Mutation(s) in the PB2 protein in the Netherlands


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