New Model to Promote Studies on the Immune System's Response to Viral Infection

A serendipitous discovery has led to the establishment of a model system for the study of viral infection based on a unique virus that infects but does not kill insect cells and is incapable of infecting cells from vertebrates.

The "Eilat virus" (EILV) was isolated more than thirty years ago from a pool of Anopheles coustani mosquitoes from the Negev desert of Israel. However, only recently has deep analysis of the sample revealed that the isolate actually contained two viruses. One was able to kill insect cells but not animal cells, while the other could infect insect cells but did not kill them. This virus could not infect animal cells at all.

Investigators at University of Texas Medical Branch at Galveston (USA) reported in the September 4, 2012, issue of the journal Proceedings of the National Academy of Sciences of the United States of America (PNAS) that phylogenetic analyses placed EILV as a sister to the Western equine encephalitis antigenic complex within the main clade of mosquito-borne alphaviruses. Electron microscopy revealed that, like other alphaviruses, EILV virions were spherical, 70 nm in diameter, and budded from the plasma membrane of mosquito cells in culture. EILV readily infected a variety of insect cells with little overt cytopathic effect. However, in contrast to typical mosquito-borne alphaviruses, EILV could not infect mammalian or avian cell lines.

Due to its unusual properties, EILV was selected as the basis for a new model system for studying serious, invective viruses. Through gene transfer proteins from other viruses, such as Chikungunya virus, Venezuelan equine encephalitis virus, Western equine encephalitis virus, and Eastern equine encephalitis virus could be expressed by EILV. These antigens were exposed to the host immune system while the virus remained unable to infect any of the host's cells.

"This virus is unique - it is related to all of these mosquito-borne viruses that cause disease and cycle between mosquitoes and animals, and yet it is incapable of infecting vertebrate cells," said first author Farooq Nasar, a graduate student at the University of Texas Medical Branch at Galveston. "We have taken the genes for the envelope proteins of very dangerous viruses like eastern equine encephalitis and used them to replace the genes for Eilat's structural proteins. That gives us viruses that we can grow in insect cells that cannot do anything in vertebrate cells at all, but still produce immunity against eastern equine encephalitis —they can be used to vaccinate animals, and hopefully someday people."

"We were extraordinarily lucky to have that other virus in our sample, because without the cell death it caused, we never would have done the work that led us to Eilat," said Farooq Nasar. "Essentially, we found it by accident. It is a gift, really, because we can compare it to other alphaviruses and figure out the basis of their ability to infect a variety of animals, including humans."

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University of Texas Medical Branch at Galveston