Searching for Answers at OSU’s Center for Veterinary Health Sciences

Friday, February 24, 2017

Clinton Jones, Ph.D. (pictured right), joined Oklahoma State University’s Center for Veterinary Health Sciences in 2015 as the Sitlington Professor of Infectious Diseases in the Department of Veterinary Pathobiology. He brought with him more than 25 years of research expertise in the field of bovine herpes virus 1 (BHV-1) and 17 years studying herpes simplex virus type 1 (HSV-1). During that time, Jones and his colleagues have made important discoveries.

“About 15 years ago, we discovered that the genes expressed during latency by BHV-1 interfere with the virus killing neurons,” explains Jones. “And specifically, this gene, a protein encoded by the virus that is expressed during latency, interferes with program cell death. This form of programmed cell death is called apoptosis. We then looked for a similar function in genes that are expressed in latently infected neurons of HSV-1 and found that HSV-1 genes expressed abundantly in latently infected neurons also encode a product that interferes with program cell death.”

According to Jones this is important because both viruses, when they establish a latent infection, need to keep the neuron alive for latency for two reasons.

“One, the virus has to stay there,” he says. “And two, neurons are terminally differentiated cells. They can never divide. So if the virus kills that cell, then it no longer has a place to have a long-term latent infection.”

Jones and his team continue even today to try and understand how this influences a long-term latent infection and how to utilize this information to make vaccines, especially against BHV-1,

that protect animals from infection but prevent latency from occurring.

“Most of our efforts are working on an animal herpes virus,” states Jones. “However, a lot of things that we find in that animal herpes virus are directly related to how human herpes viruses behave. It’s a much better system because you can use the natural host (the cow) to do experiments with. And we have discovered things in that system (BHV-1) that are very similar for HSV-1. Most the time, the virus has utilized the same kinds of pathways in the cell to achieve a latent infection or to produce virus in permissive cells.

“We work on herpes and try to understand how the virus persists in the peripheral nervous system. We are trying to develop better vaccines and understand how the virus is able to hide from the immune system while it establishes and maintains this latent infection.”

Research shows that bovine respiratory disease causes significant health concerns to the cattle industry and can result in at least $1 billion in lost production annually. BHV-1 is one of the more important viruses associated with bovine respiratory disease.  BHV-1 and HSV-1 can lead to upper respiratory tract disorders, conjunctivitis and in the case of HSV-1 can lead to corneal scarring that can progress to vision loss. BHV-1 can cause genital disorders and bovine respiratory disease.

“Bovine herpes virus and herpes simplex virus are becoming a bigger problem than it was 25 to 30 years ago,” continues Jones. “People are using modified live vaccines of bovine herpes. Although they are effective in preventing disease in adults (cows), it is also clear that they are responsible for increasing the incidence of abortions in pregnant cows. And that still continues to be a real problem.”

Jean d’Offay, BVSc, DTVM, PhD, DACVM (pictured below), professor of virology in the center’s Department of Veterinary Pathobiology, agrees whole-heartedly that vaccine-induced abortions are a problem. He has been researching bovine herpes virus since he joined the faculty in 1986. For the last 30 years or more, d’Offay has been looking at the genetics behind the disease.

“I’m just interested in virology,” says d’Offay. “I’ve worked with different viruses including AIDS-like virus in baboons. I think it’s fascinating to try and understand the genetic basis for disease. We have analyzed many BHV-1 strains—some of them are not so virulent, while others will cause serious disease. We look at the genetics between them and find out what genes might be responsible for the increased virulence of some BHV-1 strains.”

D’Offay says that once we understand that and what it is that gets the virus to cause serious disease, it will allow researchers to develop a better vaccine.

“A number of years ago, veterinarians around the country realized that the vaccine that was commercially available for BHV-1 could have caused abortions in cattle under certain conditions,” explains d’Offay. “But nobody could really prove that. It was just the fact that these animals had received the vaccine during pregnancy and then they aborted a few weeks or months later. So we started trying to understand whether we could identify the difference between the vaccine strain that was given to cattle and the wild type, which is the virus that circulates throughout and causes disease.”

D’Offay and his research team realized that most of the BHV-1 vaccines available commercially can cause abortions.

“Although the vaccine can reduce the incidence of the disease, under certain circumstances, it can cross the placenta and kill the fetus,” he says. “Additionally, when the vaccine is used in feedlots, the vaccine virus can predispose cattle to bacterial infection and results in bovine respiratory disease outbreaks.”

Bovine herpes virus 1 is easily transmissible. Cattle that are latently infected and in a feedlot setting can start secreting bovine herpes virus when stressed, which can easily spread to other cattle in the pen.

“Sometimes they get the virus very early in life like in the case of humans with cold sores who can keep having the sores throughout their lives,” continues d’Offay. “The same thing with bovine herpes virus 1. They are often infected earlier on in life and remain latently infected.  When they enter the feedlot, if they are stressed, they start secreting the virus. Now if the animals around them have never been infected, they will become sick and spread the virus to the others resulting in outbreaks of severe respiratory disease.

“I think by looking at the genes from viruses that cause severe disease and those that don’t, and looking at the genes that are present in vaccine viruses, we may get a better understanding of what is it that determines the ability of a virus to cause severe disease and what can we do to attenuate the virus to use as a good vaccine that is not going to cause abortions and not going to predispose the cattle to respiratory disease in feedlots,” concludes d’Offay.

And through the efforts of both researchers and their teams perhaps the future for the cattle industry will look a little brighter as both men continue making discoveries related to bovine herpes virus and herpes simplex virus.

For more information on Oklahoma State University’s Center for Veterinary Health Sciences, visit www.cvhs.okstate.edu.