Posted on March 15, 2004 at 4:00 p.m.

BIRMINGHAM, AL — Researchers at UAB (University of Alabama at Birmingham) have discovered the mechanism used by a common virus to replicate itself and remain in the human body for decades. Human papillomavirus (HPV), a family of over 100-related viruses, are responsible for a variety of medical conditions, ranging from benign hand or foot warts to genital warts, cervical cancer and recurrent respiratory papillomatosis, a potentially fatal disease in children.

In an article published in the Proceedings of the National Academy of Sciences in March, the research team reports that a viral replication protein known as E2 binds the circular viral DNA to cell structures called spindle fibers that are present in a cell when it divides, a process known as mitosis. In mitosis, a single cell divides in two, creating two genetically identical daughter cells. By latching onto the spindle fibers of the cell as it divides, HPV DNA also divides and replicates itself in each of the new daughter cells where it can continue to replicate and persist indefinitely.

“In effect, HPV is able to mimic our own chromosomes, behaving as a sort of ‘mini-chromosome’, independently replicating and keeping pace as the cellular chromosomes replicate and the cell divides,” says Tom Broker, Ph.D., professor of biochemistry and molecular genetics and co-author of the paper. “This allows the virus to remain in our bodies indefinitely, with the potential of causing serious disease years, even decades, after first exposure.”

Broker says that virtually all humans carry at least one type of HPV for much of their lives, usually transmitted to the external skin very early in life or to the internal mucosal lining later during sexual contact. For most people, the virus persists at low levels without causing obvious disease, and the body’s immune system keeps it in check.

However, in some people, the virus can become activated and cause lesions, particularly if the infected tissue is repeatedly injured, or following periods of emotional or physical stress, during pregnancy, as a result of immunosuppressive therapy for immune disorders or organ transplantation, as a outcome of progressing HIV/AIDS, and even as a consequence of aging.

“This is a major breakthrough in our quest to find ways to treat the myriad conditions associated with HPV,” says Louise Chow, Ph.D., professor of biochemistry and molecular genetics and co-author of the paper. “This improves our understanding of the mechanisms the virus uses to reproduce. We now have new molecular targets to aim at for antiviral drug discovery.”

HPV’s special mechanism for attaching itself to the mitotic spindles and getting pulled into the daughter cells has not been observed with other families of viruses, according to Chow.

There are about 15,000 new cases of cervical or penile cancer attributed to HPV each year in the US, and nearly 5000 deaths. Worldwide, 600,000 cases occur annually, especially in developing countries without advanced medical diagnostic methods such as Papanicolaou (Pap) smear screening, which can detect the activation of HPV early enough for aggressive treatment to be successful.

HPV infection in the throat and respiratory tract, laryngeal papillomatosis, can cause recurrent respiratory papillomatosis in children, who are usually infected at birth from contact with HPV-caused genital warts present in the mother. There are an estimated 2,000 cases per year in the United States

This research was funded by grants from the United States Public Health Service and the National Cancer Institute, one of the National Institutes of Health. Tom Broker is the President of the International Papillomavirus Society. More information on HPV and associated disease can be found at the society’s Web site at www.IPVSoc.org.

The first author of the publication is Brian A. Van Tine, for whom this project formed part of his Ph.D. thesis. Van Tine is currently completing his medical training at UAB, supported in part by the Medical Student Training Program for the M.D., Ph.D. combined degree.

The article can be read online at www.pnas.org/cgi/doi/10.1073/pnas.0306848101.