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University of Iowa News Release

June 18, 2004

UI Study Shows How Harmless Virus Helps Protect Against HIV

People with HIV who also are infected with a harmless virus called GB Virus type C (GBV-C) live longer than those infected only with HIV. Now researchers at the Veterans Affairs (VA) Iowa City Health Care System and the University of Iowa have compelling evidence of how this protection occurs at the cellular level.

The findings have implications for future studies and suggest that research designed to intentionally infect people with GBV-C warrants consideration. The study results appear in the June 19 issue of the Lancet, a leading British medical journal.

The study involved comparisons of white blood cells taken from healthy people and then purposely infected in test tubes with GBV-C and HIV or only with HIV. The team found that in cells co-infected with GBV-C and HIV two very important things happened, said the study's senior investigator Jack Stapleton, M.D. (left), a staff physician and researcher at the VA Iowa City Health Care System and professor of internal medicine at the UI Roy J. and Lucille A. Carver College of Medicine.

First, Stapleton explained, GB Virus-C increased production of protein substances called chemokines, which previous studies showed inhibit HIV. The chemokines inhibit HIV by binding to receptors normally used by HIV on white blood cells (T-lymphocytes that are part of the immune defense system). As a result, HIV cannot bind to these cells and, thus, cannot enter and multiply.

The study's lead author, Jinhua Xiang, M.D., a VA and UI research scientist and Stapleton's colleague, said, "One could think of a harbor setting where there is only one place that enemy invaders can land to unload their troops. If the dock and unloading site are blocked, then the enemy cannot invade. GB Virus-C causes the cells to produce chemokines to occupy the docking site on the T-cells, thereby making them unavailable for invasion by HIV."

Second, this chemokine inhibition causes the number of potential docking sites to decrease over time, further reducing the opportunities for HIV to get inside and multiply within immune defense cells.

"Studies over the past 10 years of people with HIV infection who survive without illness found that these patients have low levels of these docking sites on their cells, and that they have high blood levels of the chemokines," said Stapleton, who also directs the AIDS Clinic at UI Hospitals and Clinics and the UI Helen C. Levitt Center for Viral Pathogenesis. "However, in those studies nobody looked to see if the patients with HIV had GBV-C co-infection or not.

"Our data support a role for GBV-C that fits in with previous observations of these patients who are called long-term nonprogressors or slow progressors with HIV," he added.

Drugs that mimic the effect of chemokines are under investigation. However, GBV-C potentially could be used as an HIV treatment because it is known not to cause any disease, and after only a limited number of exposures, patients might see benefits.

GBV-C is a very common infection, even in healthy humans, and about one in every 50 blood donors has evidence of infection. However, because GBV-C does not cause any disease, the Food and Drug Administration has decided not to screen blood products for the virus. For this reason, plans are underway to start a clinical trial in which patients with HIV would purposely be infected with GBV-C.

In 2001 and in recent findings published in the March 2004 issue of the New England Journal of Medicine, studies involving the VA Iowa City Health Care System and UI teams helped show that GBV-C co-infection prolongs survival -- at the end of five to six-year intervals, co-infected men were nearly three times more likely to be alive than those with only HIV.

Those previous studies involved the current study's authors, Stapleton and Xiang. The recent New England Journal of Medicine study -- involving the best characterized HIV-infected people studied to date -- was led by Carolyn Williams, Ph.D., of the National Institute of Allergy and Infectious Diseases (NIAID), and included researchers from the Multicenter AIDS Cohort Study.

The study in the Lancet was supported by grants from the Veterans Affairs, NIAID, the UI Center for Research Enhancement and the UI Gene Therapy Center.

In addition to Stapleton and Xiang, the Lancet study team included Sarah L. George, M.D., former UI fellow associate in internal medicine and now assistant professor at St. Louis University; Sabina Wünschmann, Ph.D., former UI research scientist; Qing Chang, UI research assistant; and Donna Klinzman, VA research associate.

For more information about GBV-C and HIV, see this March 4, 2004 UI news release http://news-releases.uiowa.edu/2004/march/030404hiv-study.html, and this Sept. 6, 2001 UI news release http://news-releases.uiowa.edu/2001/september/0906gbv-c-virus.html.

University of Iowa Health Care describes the partnership between the UI Roy J. and Lucille A. Carver College of Medicine and UI Hospitals and Clinics and the patient care, medical education and research programs and services they provide. Visit UI Health Care online at www.uihealthcare.com.

Note to Editors: This release includes some information from a news release by Veterans Affairs.

PHOTO: A photo of Jack Stapleton is available online at http://www.int-med.uiowa.edu/Divisions/Photos/ID/JackStapleton.gif

STORY SOURCE: University of Iowa Health Science Relations, 5137 Westlawn, Iowa City, Iowa 52242-1178

CONTACTS: Media: Becky Soglin, 319-335-6660, becky-soglin@uiowa.edu;
Media: Kirt Sickels, Public Affairs Officer, Veterans Affairs Iowa City Health Care System, 319-339-7104, (cell) 319-631-0735