Key Amino Acid Behind Poliovirus Replication Identified

Penn State researchers identified a key amino acid in the polymerase of poliovirus that controls the speed and accuracy with which the virus multiplies.

The researchers say that a replacement of this key residue with different amino acids may allow them to generate such mutants of the virus as are essentially harmless.

"We found that very subtle changes in the chemistry at this location of the polymerase has dramatic effects on weakening the virus," says Craig Cameron, the Paul Berg professor of biochemistry and molecular biology at Penn State, who has a provisional patent on the technique.

"We have successfully tested this technique with poliovirus. And we think it is applicable to most other viruses," he adds.

When Cameron and his colleagues, Jamie Arnold and Christian Castro, infected mice with these mutant strains of the virus, they found that it took a lot more of the virus to sicken or kill the animals. According to Cameron, tests suggested that some viral strains with specific mutation patterns led to a form of the virus that could not sustain itself.

"By altering a single lysine residue, you not only affect the virus' replication, but also the accuracy with which it is copied. A virus’ replication speed and accuracy is optimized; there is a delicate balance. We have defined the optima for poliovirus but where that balance is going to be for different viruses, we do not yet know," he says.

Since the replication of all the viruses is regulated by a similar mechanism, the researchers feel that their discovery may represent a universal mechanism of weakening viruses that cause influenza, SARS and Dengue fever, as well as the West Nile Virus for developing vaccines.

"All standard approaches for vaccine development take years. It is all a random trial and error process to get an attenuated – weakened – virus that may be treated as a potential vaccine candidate. There is no direct method," Cameron says.

Positive strand RNA viruses, such as SARS coronavirus and hepatitis C virus, compound the problem.

"The gene makes a protein that gets processed into a lot of different functions. There is no gene to delete," Cameron says.

However, these viruses do have an amino acid similar to the residue identified in poliovirus, which can be replaced to produce weak variants, he adds.

Cameron says that the discovery may pave the way for a fast and cheap method of making vaccines. According to him, the technique of quickly creating weak viral strains for use as vaccines may also protect against viruses such as Ebola and smallpox, which might be used as biological weapons.

Source-ANI
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