Insight: Research Edition

Fall 2005

Alphaviruses Under Microscope as Concerns Rise Over Biodefense

When the United States and the Soviet Union were at the height of the Cold War, the USSR was aggressively pursuing the weaponization of biological agents that could be used in time of war to cause death and illness, create mayhem and instill fear in target populations. One such group of agents, known as alpha-viruses, showed great potential in being successful at all three mainly because some of the alphaviruses can readily be transmitted to human and animal hosts by the aerosol route of infection – a prerequisite for use as bioweapons.

When the Soviet Union broke apart and the hostilities between the United States and the former Soviet Bloc turned to cooperation, concerns over alpha-viruses faded like a bad memory. The urgency to develop effective vaccines and therapeutic agents diminished as the Cold War drew to an end. However, alphaviruses – including Venezuelan equine encephalitis (VEE) virus, Eastern equine encephalitis (EEE) virus and Western equine encephalitis (WEE) virus – are normally transmitted to their hosts by the bite of an infected mosquito and still presented a public health problem on a regional basis.

Fast forward to 2001 and the anthrax mailings that followed the terrorist attacks of September 11 – a paradigm shift was in the offing. Bioterrorism was the new catch phrase and the Department of Homeland Security wanted to make sure that research into select agents that could be weaponized, including alphaviruses, was re-energized and given greater national priority.

“We are concerned about these alphaviruses not only from a bio-defense need, but also because of emerging disease implications,” said Dr. Kenneth Olson, Director of the College’s Arthropod-Borne and Infectious Disease Laboratory. “In the 1930s and 1940s, WEE was devastating. Tens of thousands of horses died or were killed in the western United States and the disease took a toll on humans who can contract the virus as well. In the 1960s and 1970s, VEE moved from Mexico into Texas and caused a lot of problems. Right now, EEE virus is being focally transmitted in the eastern United States and is associated with high morbidity and mortality rates. Experimental VEE vaccines for use in human have been produced in limited quantities, but there are still no good human vaccines for Eastern or Western equine encephalitis.”

The difficulty in battling these mosquito-borne viruses is that they are RNA viruses. That is, the genome is RNA and RNA genomes can’t be manipulated. However, when researchers convert the RNA genome to cDNA (complementary DNA), they can then play with the genome, adding mutations to try to weaken the virus which can then be used as a vaccine. The virus will still be able to do some replication, but won’t have a disease outcome.

“Our primary goal here is to help move the process along so we can learn about the pathogenesis of the virus in a mouse model, and use that model to test vaccines or anti-viral therapies that might become available down the road,” said Dr. Olson. “The other aspect of our work is to look at the potential for infection when these alphaviruses are aerosolized. Today, we don’t know what would happen if these aerosolized viruses get into the ecosystem – how efficiently would local mosquito populations pick up the virus and begin transmitting disease? With our mouse model, we will be looking at how the virus infects and how efficient it is in causing disease when delivered by aerosol or some other method, as when com-pared to transmission by mosquitoes.”

Dr. Olson said the Regional Center of Excellence grant and the new Regional Biocontainment Laboratory will give his research group the facilities and means to move forward.

“We will now have the funds to hire the right people and provide them with the supplies they need to pursue this important work,” said Dr. Olson.“We will take what we have learned to date about arthropod-borne diseases and move that into the field of alphaviruses; not only to address the threat of bioterrorism, but also to make progress in the battle against these devastating diseases that affect humans and animals in so many parts of the world."