Converting Protein Produced by Virus into Treatment Now a Focus

AUG. 8, 2005 | A common virus with the ability to inhibit cancer in humans could lead to new treatments, says Paul Hermonat, Ph.D., the researcher at the University of Arkansas for Medical Sciences (UAMS) who has been working with the virus for more than two decades.  

Hermonat has studied the properties of adeno-associated virus type 2 (AAV-2) for more than 20 years to understand and harness the mechanisms that make the virus effective against cancer. AAV-2 harmlessly infects more than 80 percent of the population but has shown an ability to inhibit cancer development. Other viruses, such as human papillomavirus (HPV), promote the development of certain cancers.   

“AAV is the only known viral inhibitor of cancer development – meaning that this may ultimately prove to be a virus that a person will be glad to be infected with,” said Hermonat, a professor of internal medicine in the UAMS College of Medicine. “Continuing research by our team has shown that the relationships between AAV and HPV in the cell are complex but show promise as a cancer treatment.” 

Hermonat’s group first identified the Rep78 protein produced by AAV as the anti-cancer component. Production of Rep78 in effective quantities is one obstacle to developing a new treatment; along with understanding the complex interactions that make the virus inhibit cancer development.   

The inhibition of cancer development occurs mostly on the level of gene expression, Hermonat said. Not only does Rep78 inhibit HPV from expressing its cancer-causing genes but it also inhibits many cellular genes known to be involved in cancer.

Studies dating back to the 1970s suggested that AAV-2, found naturally in the female genital tract, inhibited cancer development. Later research showed that HPV, which causes warts, is also a factor in the development of cervical cancer.  

Hermonat is in the second year of a five-year, $1.2 million grant from the National Institutes of Health to find the genes present in HPV that help replicate AAV-2 and to better understand the interactions between the two viruses.  

The two viruses are often found together but appear to affect one another in different ways depending on the volume of each virus present. Low amounts of AAV actually stimulate higher HPV replication, Hermonat said, while high amounts of AAV hamper HPV replication. 

Among the pending patents based on his AAV research, Hermonat has applied for a patent on the AAV Rep78 protein and its use in gene therapy and anti-cancer treatments. Hermonat was also a lead scientist in the first investigation into the use of AAV as a gene therapy vector, meaning it could be modified to carry genes designed as medical treatments into the body. 

AAV has looked to be a top gene therapy vector since it is harmless to healthy cells – even while it has shown the ability to limit cancer. 

UAMS is the state’s only comprehensive academic health center, with five colleges, a graduate school, a medical center, five centers of excellence and a statewide network of regional centers. UAMS has more than 2,200 students and 660 residents and is the state’s largest public employer with almost 9,000 employees. UAMS and its affiliates have an economic impact in Arkansas of $4.1 billion a year. 

UAMS centers of excellence are the Arkansas Cancer Research Center, Harvey and Bernice Jones Eye Institute, Donald W. Reynolds Institute on Aging, Myeloma Institute for Research and Therapy and Jackson T. Stephens Spine & Neurosciences Institute.