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Nov. 17, 2014

Prof Barik receives grant to research pediatric virus

By Dan Levindofske

Cleveland State University professor Sailen Barik has been awarded a $400,000 National Institue of Health grant to conduct research on respiratory syncytial virus, commonly known as RSV, which is a highly infectious respiratory virus that causes severe disease in infants. The virus is also prevalent in the elderly population, as it affects those with weak immune systems.

Barik said that all infants get exposed to RSV but most are strong enough to overcome it. Those who suffer complications from it are not only at risk when they are babies, but are also more likely to developrespiratory disorders such as asthma in adulthood.Dr. Sailen Barik

“If children were infected early in childhood with RSV — most of them will recover and they will grow up to be adults — they may be predisposed or more susceptible to asthma than if they were not infected,” Barik said.

RSV does not promote stable immunity to those who have it either, so it is possible to get it multiple times in one’s lifetime.

“It does not produce lasting immunity, unlike some other viruses,” Barik said. “People with an RSV infection can get re-infected in a couple months, again and again and again.”

There were clinical trials around 1969 — conducted by the pharmaceutical company Pfizer — to find a vaccine for RSV, but they had disastrous results, even causing two deaths, which was an unexpected phenomenon that came to be known as “vaccine-enhanced disease.” Since then, extreme caution is being exercised in RSV vaccine development, according to Barik.

“There’s a big scare about even trying an RSV vaccine because we’re talking about children here — babies,” Barik said. “Once in a while people have tried different experimental formulations, but nothing really worked well or without adverse reactions.”

Barik explained that the RSV virus differs from most other viruses in that it affects a segment of the population that has too weak of an immune system for vaccines to be effective.

“If natural immunity doesn’t work if it’s not long lasting — does that mean that even if we spend billions of dollars to come up with a man-made vaccine of some kind, do we have to vaccinate people every month,” Barik asked.

Barik’s main focus is on an alternative approach, which is to find an adequate treatment for RSV by inhibiting the nonstructural genes of RSV that shuts off the immune system’s ‘alarm.’ This is a newer approach that hasn’t been attempted very often when trying to combat viruses.

“We have found that there are two RSV proteins,” Barik said. “They are called NS — for nonstructural — and they degrade some of these antiviral proteins of the host cell.”

It wasn’t until a few years ago that Barik discovered how these NS proteins suppressed the interferon response of our immune system. Interferons act as an alarm system within the body to fight off infections.

“Interferon production is triggered by the infection and it then acts on the neighboring uninfected cells — that are not infected yet — and makes those cells virus-resistant by activating the production of many antiviral proteins,” Barik said.

Barik described that the suppression of the interferon response occurs through the degradation of the antiviral proteins — promoted by the NS proteins — and that his laboratory is busy figuring out how NS proteins actually do it.

“There are diverse mechanisms by which the NS proteins rob the immune bank, so to speak,” Barik said. “Some kill the guards, some climb the roof or dig holes underground. There are many ways in which viruses try to defeat different arms of innate immunity, and RSV NS proteins are experts in this business.”

This is a severe situation, and the cost of RSV-related hospitalization alone is nearly $1 billion a year, according to Barik.

“Although the exact number of RSV deaths remains unknown, it is estimated to be in the order of millions worldwide,” Barik said.

“It’s a huge public health problem,” Barik said. “There are conferences on it and every major biopharmaceutical company has tried to come up with a vaccine or antiviral against RSV over the last 20 or 30 years, maybe even 40 years — and they all failed.”

Barik believes that if they can discover a way to cripple the NS functions of RSV, they will have a real way to fight the virus.

“If we find out how these viral entities, such as RSV NS proteins, defeat the interferon system then that could be a viable approach in which we can find countermeasures to defeat the viral proteins that defeat the interferon system,” Barik said.