Poliovirus is IRESistable

Our latest paper has just been published in the Journal of Clinical Investigation. The title of the paper is “Poliovirus tropism and attenuation are determined after internal ribosome entry”. This is the work of a Ph.D. student in my laboratory, Steven Kauder.

If you would like a nice summary of this work, there is an excellent commentary by Bert Semler in the same journal, entitled “Poliovirus proves IRES-istible in vivo“. The title of this commentary is a play on the main theme of the research paper: the Internal Ribosome Entry Site (IRES) of poliovirus. The poliovirus IRES is an RNA sequence at the 5′-end of the viral genome that allows ribosomes to bind internally, rather than threading on the 5′-end as they do for most mRNAs. In our paper, we show that poliovirus attenuation and tropism are not determined by the viral IRES.

Let’s back up a bit to explain this last statement. Viral tropism is defined as the tissues in which a virus replicates. Poliovirus, the causative agent of poliomyelitis, infects very few tissues in humans: the intestine, the brain and spinal cord, and perhaps one other site. A restricted tropism is in fact a common property of many viruses. What restricts viral multiplication to so few tissues has been a long-standing question in virology. For poliovirus, it was first believed that the restricted tropism was a consequence of where the virus receptor is located. The virus receptor is a cell surface protein that is needed to bind the virus particle and bring the genetic material of the virus into the cell. However, some time ago it was shown that the receptor for poliovirus does not determine the narrow tropism of the virus. Subsequently it was suggested that the viral IRES might control the tropism – but in this recent paper we show that this is not the case.

The other topic of our paper concerns the live poliovirus vaccine, also known as the Sabin vaccine or oral poliovirus vaccine (OPV). There are three different vaccine strains of poliovirus, all isolated by Albert Sabin. The genetic material of each vaccine strain contains mutations, or genetic changes, that prevent it from causing disease. When the Sabin vaccines are ingested, they replicate in the intestine and provide immunity to infection, but they do not cause polio. Precisely how these mutations ‘work’ has been a matter of considerable debate. It has been believed that the mutations change the properties of the viral IRES so that it continues to direct translation in the human gut, but not in the spinal cord and brain. In our paper we show that this hypothesis is wrong. A mutation in one of the three Sabin vaccine strains actually weakens the virus in all tissues.

I recognize that much of this description may be beyond the understanding of someone who is not a scientist. A goal of this weblog is to make virology accessible to everyone. Therefore in the coming weeks I will endeavor to provide the background needed to understand this and similar material that will appear here.