These University of Michigan scientists have discovered how some viruses can hide inside the nucleus of human cells for long periods of time---without producing symptoms or triggering an immune response---by attaching to host cell chromosomes. The virus survives by going dormant until a weakened immune system allows infected cells to begin multiplying wildly again.
In an article to be published in the Nov. 25, 1999, issue of Virology, Robertson and Cotter describe a series of experiments with Kaposi's sarcoma-associated herpesvirus or KSHV---a human virus associated with a type of cancer called Kaposi's sarcoma. In these studies, U-M scientists found a protein expressed by one gene on the virus that builds a biochemical docking station linking viral DNA to the chromosomes of lymphoma cells. The U-M study is the first to identify a specific tethering mechanism between a virus and its host cell.
KSHV, also known as human herpesvirus 8, is one of a family of gammaherpesviruses known to remain dormant in humans long after the initial infection is over. Other similar viruses include the Epstein-Barr virus, the human papilloma virus which causes cervical cancer, and viruses responsible for hepatitis B and hepatitis C.
"We've always suspected that latent viral DNA couldn't survive long term within cells without some type of tethering," said Robertson, Ph.D., assistant professor of microbiology and immunology in the U-M Medical School. "But the latency mechanism for these viruses has been a black box. Now we have a key that will get us in the front door."
Using cultures of lymphoma cells infected with KSHV, Cotter and Robertson identified a protein called the latency-associated nuclear antigen or LANA, which is expressed by one of approximately 80 genes encoded by the virus. They found that LANA binds to three regions of the KSHV genome
Contact: Sally Pobojewski
University of Michigan