MadSci Network: Virology
Query:

Re: Is it possible to cure a filovirus by using one of its sisters?

Date: Wed Aug 20 16:00:49 2008
Posted By: Dean Cliver, Faculty, Food Safety Unit, Uiversity of California, Davis
Area of science: Virology
ID: 1217438825.Vi
Message:

This certainly is not a silly question. Closely related viruses are sometimes used to make vaccines, as in the case of vaccinia (cowpox?) virus that was used to eradicate smallpox. However, this depends on an immune response, which is relatively slow, so vaccination is best done before exposure to the disease agent. Sometimes, viruses can interfere with each other during a concurrent infection; the host cell "manufactures" (synthesizes) all of the components that become the progeny viruses. In an interference situation, one virus corrupts production of the components of the other virus by the cell. This seems to be what you have in mind with Ebola Reston, and it would probably work if the virus were able to enter every cell that was infected with Ebola Zaire. The great challenge is getting the Reston strain to chase the Zaire strain in an infected host.

However, what is being done that shows considerable promise is not too different from what you suggest. As you know, the genetic information in the Ebola virus is in the form of minus-sense RNA. In order to take over a host cell, this minus-sense RNA must first be transcribed into plus-sense RNA, by means of an enzyme that the virus brought with it. Then, the plus-sense RNA can serve as messenger and be translated into all of the virus-specific proteins by the cell. If minus-sense RNA from the Reston strain got into a cell that was infected by the Zaire strain, it is possible that homologous portions of the minus-sense RNA from Reston would block translation of those genes on the plus-sense RNA of the Zaire strain. Getting intact Reston RNA in where it was needed would be a great challenge.

Instead, a similar blockage of translation is being done with anti-sense oligomers. These are short lengths of RNA that have been designed to block key virulence genes in the Ebola virus. Because RNA is easily destroyed, these are stabilized by modifying them chemically, so that they are not affected by RNase. The two Warfield references listed below give many more details. It appears that as many as three genes may need to be targeted at a time, and that the treatment may save a significant portion of infected rodents and monkeys. At what point it will be possible to test this in infected humans is not stated.

In any case, it seems likely that the rationale for this approach started with an idea rather similar to yours. With more training in science, you should be able to make contributions of your own.

Dean O. Cliver

References:
http://en.wikipedia.org/wiki/Ebola

Warfield, K. L., D. L. Swenson, G. G. Olinger, D. K. Nichols, W. D. Pratt, R. Blouch, D. A. Stein, M. J. Aman, P. L. Iversen, and S. Bavari. 2006. Gene-specific countermeasures against Ebola virus based on antisense phosphorodiamidate morpholino oligomers. PLoS Pathog 2:e1.

Warfield, K. L., R. G. Panchal, M. J. Aman, and S. Bavari. 2006. Antisense treatments for biothreat agents. Curr Opin Mol Ther 8:93-103.


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