GB Virus C – potential as an HIV therapeutic?

Today I read a paper and an opion piece from advance access for the journal Clinical Infectious Disease discussing GB virus C (GBVC) and its’ role in HIV infection. The opinion piece argued that GBVC should be used as a biovaccine in patients with HIV, because clinical data has demonstrated that those people coinfected with GBVC and HIV have a better prognosis than those with HIV alone.

GBVC infection is common and occurs worldwide. It is estimated that 1-5% of healthly blood donors in developed countries, and up to 20% in developing countries have replicating virus at the time of donation. GBVC has not been associated with any disease. In fact, blood donations are not screened for presence of GBVC because no known diseases occur in those that are infected.

GBVC infection has been associated with prolonged survival in HIV positive people, causing a 2.5 fold reduction in mortality during later (>5 years) stages of HIV infection. In addition, those people coinfected have higher CD4+ T cell counts, lower HIV viral load, delayed progression to AIDS, improved response to antiretroviral therapy, and reduced mother-to-child transmission.

The mechanism(s) used by GBVC to modulate HIV infection haven’t been fully elucidated, but appear to be numerous. GBVC infection alters the expression of HIV entry receptors, and causes the secretion of the natural proteins that bind to the receptors, making it very difficult for the virus to spread to uninfected cells. GBVC infects the same cells that HIV infects, and some of the proteins of GBVC are able to inhibit replication of HIV. Without replication, the virus is unable to make copies of itself, and spread throughout the body. Another protein from GBVC appears to directly interact with HIV, preventing the virus from entering new cells. Most of this should occur when GBVC is actively replicating. Once GBVC virus has been “cleared”, antibodies against the viral protein E2 appear. These antibodies can bind to either a cellular or viral target (it’s not known which) and prevent HIV entry into cells. GBVC is able to alter innate and adaptive immunity, which can help aid the anti-viral immune response to HIV infection. Combined, all of these effects of GBVC lead to improved prognosis for people with HIV infection.

The opinion piece makes a lot of valid points – if GBVC is harmless (and it certainly appears that way) then studies should be undertaken to determine if infecting HIV positive people with GBVC will be a successful therapeutic option. All the data so far points to yes.

For more information see:

Vahidnia et al. “Acquisition of GB Virus Type C and Lower Mortality in Patients With Advanced HIV Disease” Clinical Infectious Diseases

David Gretch “Advocating the Concept of GB Virus C Biotherapy Against AIDS” Clinical Infectious Disease

For lots of research and reviews, look up Jack T Stapleton