Arteriviruses in pigs, horses, mice, and apes appear to use the same non-specific protein to evade the body’s immune system
From the common cold to HIV, many illnesses—in fact, more than 90 percent of human illnesses—are caused by viruses.
In the war against viruses, medical researchers called virologists are constantly seeking new avenues of attack. Vaccinations to provide immunity against infection constitute one of virologists’ most effective weapons for controlling viral disease.
The viruses, on the other hand, are continuously changing genetically; changes that help the virus outsmart the immune system of the host, and thus help the virus to survive and spread, lead to new viral strains to be battled.Dr. Dongwan Yoo, a virologist in the Department of Pathobiology, uses reverse genetics to figure out, at the molecular level, the strategies that viruses use to evade the host’s immune surveillance system.
Dr. Yoo is one of the world’s foremost authorities on the porcine reproductive and respiratory syndrome (PRRS) virus. PRRS takes a big toll economically in pig-producing countries worldwide. In the United States alone the economic losses attributable to PRRS are estimated at $660 million per year.
Unfortunately, the PRRS virus has proven especially tricky when it comes to developing a vaccine against it. The PRRS vaccines currently available are less than satisfactory, and Dr. Yoo’s research is focused on understanding virus-host interactions in order to find strategies for more efficacious vaccines in arteriviruses, the group of viruses that includes PRRS.
Arteriviruses are closely related to coronaviruses, a family of viruses that infects mammals and birds and includes severe acute respiratory syndrome (SARS) in humans, feline infectious peritonitis (FIP) in cats, and infectious bronchitis in poultry.
“Innate immunity is the body’s first line of defense against viral infection,” says Dr. Yoo. “Viruses such as PRRS have evolved to evade detection by the immune system, allowing the virus to persist in the body and result in chronic infection. I am working at the molecular level to identify how this virus evades the immune system.”Normally when cells in the body are infected by pathogens, the cells release interferons, components that “interfere” (hence the name) with virus replication to help the body fight off the infection.
“More than 300 antiviral proteins are believed to be produced through the interferon system, providing an essential defensive unit of the innate immune system. Interferons also play a role in the body’s ability to acquire immunity to pathogens,” says Dr. Yoo.
Using reverse genetics, Dr. Yoo’s research team generated genetically engineered mutant viruses to investigate the role that individual viral proteins play during infection. They identified at least three non‑structural proteins and one structural protein in the PRRS virus that aid in interferon suppression, meaning that these proteins somehow reduce the body’s production of interferons during infection.
“When interferon production is suppressed, hosts are unable to eliminate invading viruses effectively, and viruses may survive longer in the body, which means there may be more opportunity for the viruses to be transmitted to other animals,” explains Dr. Yoo.
Recently, Dr. Yoo and his team expanded their study to include three other arteriviruses: equine arteritis virus (EAV), murine lactate dehydrogenase-elevating virus (LDV), and simian hemorrhagic fever virus (SHFV).
“Our hypothesis was that arteriviruses may use a common strategy for interferon suppression during infection. Since nsp1 (non-structural protein 1) plays the biggest role in interferon suppression in the PRRS virus, we cloned the nsp1 gene from all four arteriviruses and examined their interferon-suppressive function in cells,” says Dr. Yoo.
They found that, for all the arteriviruses, nsp1 did inhibit the cells’ interferon production. However, it also appeared that the mechanism of action for interferon suppression, as well as the genomic structures of the viruses, differed among the four arteriviruses.
“This information may become the basis for future vaccine development, not only for PRRS but also for related viruses,” explains Dr. Yoo. “Once we have a better understanding of such viral strategies, the virus’s ability to alter host immunity can be eliminated from the virus. This understanding will help us design new generation vaccines.”
This research was published as Biogenesis of non-structural protein 1 (nsp1) and nsp1-mediated type I interferon modulation in arteriviruses. Mingyuan Han, Chi Yong Kim, Raymond R.R. Rowland, Ying Fang, Daewoo Kim, Dongwan Yoo. Virology 458-459 (2014) 136–150.
Article by Melissa Giese, Class of 2017