Alcohol Researchers Show "Friendly" Virus Slows HIV Cell Growth
A team of alcohol researchers led by Jack Stapleton, M.D., of the Department of Internal Medicine, University of Iowa College of Medicine and the Iowa City Veterans Affairs Medical Center, report in the September 6 New England Journal of Medicine, Volume 345, 2001 ( Effect of co-infection with GB virus type C (Hepatitis G Virus) on survival of HIV-infected individuals: In vitro co-infection suggests inhibition of HIV replication by GB virus C) that GB virus type C (GBV-C) appears to have retarded the progression of human immunodeficiency virus in a 12-year clinical study of HIV patients. Using an infectious molecular clone of GBV-C, the same team showed in a laboratory study that GBV-C reduces the growth rate of HIV in cultured human T-cells, a form of white blood cells or lymphocytes.
The clinical finding came while Dr. Stapleton and his colleagues explored relationships among alcohol, seronegative hepatitis C virus (HCV) infection, GBV-C infection, and liver disease in patients of the University of Iowa HIV/AIDS Clinic. Damaging effects of alcohol on immune function, including effects in patients with HIV and AIDS, are a longstanding focus of alcohol research.
In the study population of 362 HIV-infected patients, 144 (39.7 percent) were co-infected with GBV-C, a proportion similar to that of GBV-C co-infection among all HIV patients. Originally known as hepatitis G, GBV-C also infects about 15 percent of patients with hepatitis C. Unlike hepatitis C, however, GBV-C causes neither hepatitis nor any other clinical symptoms.
"From several earlier studies that examined the relationship of HIV and GBV-C, we suspected that GBV-C might exert a positive effect toward slowing the progress of HIV infection. We expanded the previous research by looking at a very large group of patients followed at our clinic between 1988 and 2000 and found that HIV-infected people without GBV-C infection were 3.68 times more likely to die than those with GBV-C," Dr. Stapleton said. "This leads us to believe that GBV-C is one factor explaining how some people live longer and more healthily with their HIV infection than other HIV-infected people do."
The laboratory component of the study used an infectious molecular clone of GBV-C and HIV culture systems developed by Jinhua Xiang, M.D., and Sabina Wũnschmann, Ph.D., in Dr. Stapleton's University of Iowa laboratory and at the Iowa City Veterans Affairs Medical Center to demonstrate that, like HIV, GBV-C grows in CD-4 positive "helper" T-cells. In a series of experiments to determine if GBV-C altered HIV replication in vitro, the researchers tested the production of p24 antigen, a marker of HIV growth, in cell cultures infected with HIV alone, GBV-C alone, and both HIV and HGV-C. They found that cells infected with both viruses produced 30 to 40 percent less HIV than those infected with HIV only.
"We are now working to understand precisely how GBV-C inhibits HIV from growing," Dr. Stapleton said. "We do not know whether GBV directly interferes with HIV, or if the GBV stimulates cellular proteins, such as interferon or immune cytokines, that protect the cells against HIV growth."
Understanding the mechanism by which GBV-C retards HIV progression holds promise for designing new treatments that will prolong life for HIV-infected patients. "It may be reasonable to consider using GBV-C as a novel therapeutic vector to delay disease progression," Dr. Stapleton said.
"Alcohol is toxic to every organ system. Hence, alcohol research spans the spectrum of biomedical research," said NIAAA Director Enoch Gordis, M.D. "It is gratifying when the work of alcohol researchers sheds light on diseases other than alcoholism-especially diseases with consequences to individuals and society such as those of HIV-AIDS, the most far-reaching epidemic of our time."
For an interview with Dr. Stapleton, please telephone 011-33-1-47-05-46-21 through September 4 or Becky Soglin, Health Science Relations, University of Iowa (319/335-6660). For an interview with Dr. Gordis, telephone the NIAAA Press Office (301/443-0595 or -7351). Additional alcohol research information is available at: http://www.niaaa.nih.gov/research.