Scientists still have a lot to learn about herpesviruses and how they establish infection. Host cells naturally have antiviral defence strategies to prevent infection, and viruses must counteract these cellular defences in order to produce and release new infectious virus. One major question that remains unanswered is how herpesviruses can counteract a host’s antiviral defence that’s aimed at blocking a critical step of virus replication — the expression of viral proteins.
A research team at the Western College of Veterinary Medicine (WCVM) is focused on solving this mystery — discovering answers that may lead to new treatments for herpesviruses that infect humans as well as other species, such as cattle and horses.
For example, bovine alphaherpesvirus 1 (BoHV-1) infects cattle and can spread throughout a herd. It causes a range of health problems including respiratory tract disorders (it contributes to bovine respiratory disease complex or “shipping fever”), pink eye (conjunctivitis), abortions and genital disorders.
Although vaccination can reduce symptoms and transmission of BoHV-1, the virus remains latent in infected animals for their lifetime. Stress can cause the virus to reactivate and cause disease within the infected animal, and it can spread and infect other cattle in the herd.
Led by Dr. Kristen Conn (PhD), WCVM researchers are focused on understanding how viral protein expression is regulated. Cells attempt to silence herpesvirus protein expression by promoting the stable binding of cellular proteins called histones with viral DNA. This complex of histones and DNA, called chromatin, regulates access to the DNA.
Herpes simplex virus 1 (HSV-1) expresses a protein called ICP4 (infected cell polypeptide 4) that is absolutely required for the production of new infectious HSV-1 virus. The researchers are investigating ICP4’s power to alter how histones interact with DNA in order to disrupt the host cell’s ability to fight against herpesvirus infection.
“Why ICP4 has this function is not yet known,” says Conn, an assistant professor in the WCVM’s Department of Veterinary Microbiology. “[My current goal is to] characterize the molecular mechanisms whereby ICP4 regulates histone chromatin exchange. That way, we can understand the importance of this ICP4 function for HSV-1 protein expression and and replication.”
Conn’s previous research focused on HSV-1 that infects people and causes oral and genital herpes infections. She expanded her research program to also investigate the chromatin regulation of BoHV-1 and equine alphaherpesvirus 1 (EHV-1) after joining the WCVM’s faculty in 2018.
Conn’s past work with HSV-1 has been a good starting point for her investigations of BoHV-1 and EHV-1. She first discovered that histone association with DNA is altered during HSV-1 infection while completing her PhD degree in biochemistry at the University of Alberta.
Conn’s work on veterinary herpesviruses is only beginning, but her investigations of BoHV-1 and EHV-1 replication may have a significant impact on future antiviral drugs and treatments that can help cattle, horses and people alike.
Conn’s herpesvirus research is supported by the Saskatchewan Health Research Foundation, the Natural Sciences and Engineering Research Council of Canada, and the Townsend Equine Health Research Fund.
Kornelia Kaminska of Saskatoon, Sask., is a third-year student in the University of Saskatchewan’s College of Arts and Science who worked as a summer research student in 2021. Her story is part of a series of articles written by WCVM summer research students.