The Good Housekeeper: GBV-C Co-infection with HIV

Body Horrors
By Rebecca Kreston
May 3, 2012 2:27 AMNov 20, 2019 12:29 AM


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I know that the study of infectious diseases seems grim. Bacteria are increasingly becoming antibiotic resistant, baby parasites nest in your brain and tuberculosis spreads to your toes. I get it - all this devotion to the study of what gruesome-thing-du-jour is in your blood and saliva isn't sunshine, puppies and rainbows. So in the interests of maintaining public optimism, I offer you GBV-C, a virus that has been found to offer a protective, antiviral effect against HIV infection. Yes, that HIV.

GBV-C is a member of the Flaviviridae family of viruses; a truly distinguished and deadly lot that includes hepatitis C, yellow fever, West Nile virus, dengue and a slew of nasty encephalitis-causing viruses that roost in mosquitoes and ticks. GBV-C, however, appears to exist within the body as a benign, harmless infection. It provokes no identifiable clinical symptoms of disease and seems to be the black sheep of the noxious Flaviviridae family (2).

The one thing that makes this virus notable, even outstanding!, is that for those who are co-infected with HIV and GBV-C have been shown to live significantly longer than those without GBV-C (3). If HIV is an unwelcome houseguest in the human body, then infection with GBV-C is like waking up one day and unexpectedly finding a housekeeper doing the dirty dishes and containing the mess created by this destructive guest.

A model showing the morphology of the GBV-C virus. The human body's antibody to the E2 envelope glycoprotein may assist in stymieing HIV infection. Source: the Physician Research Network. Click for source.

GBV-C is spread in ways similar to the transmission of HIV: through sex, birth and blood. Human infection with this virus is common, with 1–8% of healthy blood donors showing evidence of infection worldwide (1). So common in fact that isolated indigenous populations in Papua New Guinea have been found to harbor the virus (3). The global distribution and evolution of the major genotypes of this virus echoes human migration patterns, indicating that this is one old viral dude that’s been hitchhiking along with humans for millions of years (3).

GBV-C provides a beneficial, antiviral effect by stymieing HIV’s advances into immune cells and spurning its replication efforts in the body. It does so in a dizzying number of ways (reader beware: it’s gonna get molecular up in here). The infection stimulates messenger signals known as cytokines to activate a cellular response and consume HIV infected cells (otherwise known as the T helper 1 (Th1) cellular response system). The virus also encourages the innate immune response by boosting pathogen-fighting interferons; this innate response can be considered one of the “first responders” of the immune system as it responds to nearly every type of infection while also activating the more advanced components of the immune system to respond to any bacterial/viral/protozoal invaders.

GBV-C stops the human cells that HIV infects, CD4+ T cells, from killing themselves in the programmed-cell-death process known as apoptosis. Apoptosis is induced by HIV-infected T cells and can affect uninfected and infected cells alike; GBV-C protects these cells maintaining their population levels. This discovery is particularly noteworthy as a crash in the population of CD4+ T cells (“CD4+ counts”) is a hallmark of immune deficiency and disease progression from HIV to AIDS.

On the left, a T cell is covered in budding HIV virus particles and will soon undergo programmed-cell-death or apoptosis. On the right, a close-up of the budding virions. Infection with GBV-C may halt this process and prevent a population crash in the numbers of CD4+ cells. Image source: Roingeard P & Brand D (1998) Budding of Human Immunodeficiency Virus. N Engl J Med. 339(32). Click for source.

The GBV-C virus causes a decrease in the cellular presence of the receptors that HIV uses to gain entry into the cell (in science speak: there’s a down-regulation of the CCR5 and CXCR4 chemokine receptors); this is akin to temporarily removing the doors of your house to predators and thieves instead of just locking them shut. In addition, GBV-C infection seems to decrease the presentation of special “activation markers” on the surface of T cells, interfering with signaling pathways that activate the production of T cells (2). Unfortunately, it’s not entirely clear what effect this “reduced immune activation” has on the immune system and whether this assists or hinders the immune system’s response to HIV infection. Certain proteins produced by GBV-C also inhibit HIV replication (1)(3).

Overall, co-infection with the two viruses leads to increased survival of HIV-infected patients and decreased mortality (1). Not too shabby! How it does this is largely uncertain - is it due to the presence of GBV-C virus particles (known as viremia) or the body’s response to GBV-C infection and its concomitant production of antibodies against the GBV-C virus (namely the anti–GBV-C envelope glycoprotein (E2) antibody)? The fact that 15-43% of HIV-positive people show active GBV-C infection and that another 31-55% show evidence of previous infection makes it difficult to disentangle these two questions (1). However, by all accounts, what we have here looks like a symbiotic relationship between GBV-C and humans.

Two researchers behind most of the work into GBV-C have suggested that this delightful house keeper may more accurately be called the "good boy virus", a phrase that heartily captures its place in a HIV-positive body (2). The Flaviviridae family needs all the good PR it can get and this GBV-C do-gooder might be the trick.

Though it’s unlikely HIV physicians are going to start recommending GBV-C infection to HIV-infected patients anytime soon, the work of this benign virus has intriguing implications for future virology research. Study of the virus’s housekeeping efforts may yield new targets for anti-HIV medications and alternative avenues for future research. Perhaps this virus could even be genetically-modified to magnify its HIV-fighting ways and be employed as a form of HIV treatment? We already do the opposite of this with many virulent pathogens, using weak or killed viruses as vaccines, and there are physicians out there that advocate for the use of bacteria-killing viruses; using bacteriophages to fight stubborn infections was an especially popular treatment in Eastern Europe and the former Soviet Union in the 1950s (4). In the face of mounting antibiotic resistance across the globe, using do-gooder viruses like GBV-C may soon be the only option we have left.


The United State’s FDA does not screen donated blood for GBV-C. Dozens of studies have failed to find any link whatsoever between GBV-C infection and disease and, as such, an estimated 1000 Americans a day receive blood with GBV-C virions or antibodies (2). I covered blood screening for infectious diseases in this article here.

The Phage Therapy Center in the Republic of Georgia is the pioneer in providing bacteriophage treatment for a smorgasbord of bacterial infections.

A 2006 review looks at natural resistance to HIV in certain individuals, whether that be from GBV-C, the host immune response or host genetics. It’s free!

References 1. Xiang J et al. (2004) Inhibition of HIV-1 replication by GB virus C infection through increases in RANTES, MIP-1, MIP-1, and SDF-1. Lancet. 363(9426): 2040-6 2. Bhattarai N & Stapleton JT. (2012) GB virus C: the good boy virus? Trends Microbiol. 20(3):124-30 3. Polgreen PM et al. (2003) GB virus type C/hepatitis G virus: a non-pathogenic flavivirus associated with prolonged survival in HIV-infected individuals. Microbes Infect. 5(13): 1255–1261 4. Sulakvelidze A et al (2001) Bacteriophage Therapy. Antimicrob. Agents Chemother.45(3): 649-659. Accessible here.

Polgreen, P., Xiang, J., Chang, Q., & Stapleton, J. (2003). GB virus type C/hepatitis G virus: a non-pathogenic flavivirus associated with prolonged survival in HIV-infected individuals Microbes and Infection, 5 (13), 1255-1261 DOI: 10.1016/j.micinf.2003.08.006

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