Infection with GBV-C linked to longer life
Odd benign virus is related to hepatitis C
New research has established a link between HIV patients being infected with a virus that is similar to hepatitis C and having a slower HIV disease progression. Investigators first began to look at GBV-C in the mid-1990s as a possible cause of chronic hepatitis, but they quickly lost interest when the virus was shown to have no direct link to the disease, says Jack Stapleton, MD, a researcher and physician at the Veterans Affairs Medical Center in Iowa City, IA, and a professor of internal medicine at the University of Iowa in Iowa City.
"The virus was discovered in late 1995, and by 1998 it was determined it didn’t cause hepatitis, so most people quit studying it," Stapleton says. "But we’re slow, and we had some interesting questions about the virus, and so we continued to work on it."
Stapleton and fellow investigators searched for differences between GBV-C and hepatitis C in an effort to understand how hepatitis C causes hepatitis. Their other goal was to examine GBV-C for use in gene therapy. "The virus is a persistent and common human infection that doesn’t cause disease," Stapleton explains. "So we reasoned that it might be useful as a gene therapy factor as a way to express foreign genes."
GBV-C is a bloodborne virus that is more efficiently transmitted sexually than hepatitis C, Stapleton says. "People who have sexually transmitted diseases have a higher rate of infection of GBV-C than the general population, and the virus is easy to transmit from mother to child."
Then in 1999, the investigators came across reports by German and Japanese researchers. They found that people who are infected with HIV and co-infected with GBV-C had better clinical outcomes than HIV patients without GBV-C infection. "One of my projects was to look at hepatitis C and GBV-C in HIV-positive people to look at different issues related to viruses and responses," Stapleton says. "Somewhat to our surprise, when I looked at patients who were in the clinic for more than 10 years — the first 14 patients — 13 of them had GBV-C infection."
The investigation changed focus and began to involve a look at samples from HIV patients that dated back to 1988. Researchers studied blood samples and mortality data from 362 HIV patients, including 144 who had a GBV-C co-infection. Of the 144 people co-infected with HIV and GBV-C, 28% had died, compared to deaths among 56% of those with HIV and no GBV-C infection. The study also found that nearly 40% of the HIV patients studied had GBV-C co-infection, while in the United States, among healthy blood donors, only 1.8% of people are infected with GBV-C.1 "When we looked at their CD4 cell counts, treatment, prophylaxis, parameters, and survival, we found that the group with the GBV-C co-infection had a much lower death rate," Stapleton says. "It really was quite striking."
Armed with more information, researchers returned to the lab and examined the cells infected with GBV-C to see if they could measure any differences between cells lacking the co-infection. It was possible that GBV-C co-infection had nothing to do with prolonged survival with HIV disease and that the coincidence had some other explanation, Stapleton notes. However, lab tests showed that cultured human T-cells co-infected with GBV-C had less HIV cell growth than those that didn’t, Stapleton says. "An explanation is that GBV-C is damaging cells somehow, or maybe it’s preventing cells from metabolizing protein as fast," Stapleton explains. "We think GBV-C is somehow acting to inhibit HIV from growing."
When researchers infected cells with HIV for 24 hours before inserting GBV-C, they saw that GBV-C inhibited HIV as much as if the cells were infected with both viruses simultaneously, Stapleton says. "This argues to us that GBV-C is altering cells in some way to make them less hospitable for HIV," he says. "What we don’t have evidence for is whether the cells infected with GBV-C are the same as those infected with HIV, and that would be a prerequisite for this to be a direct interference."
There are indirect ways a virus can induce protection, Stapleton adds. "For example, some studies show influenza virus infections and vaccination can make T-cells secrete interferon and be less susceptible and hospitable for HIV." An alternative theory is that GBV-C is altering cytokine expression within cells, making them less hospitable for HIV, Stapleton says. "These are substances that can be released by cells and affect surrounding cells and still have an inhibitory effect, — even if the same cells are not infected," Stapleton explains. "We’re actively studying this to find out which substances those are, and we’re leaning toward that explanation."
Reference
1. Xiang J, Wunschmann S, Diekema DJ, et al. Effect of coinfection with GB virus C on survival among patients with HIV infection. N Engl J Med 2001; 345(10):707-714.
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