|LETTER TO EDITOR
|Year : 2018 | Volume
| Issue : 2 | Page : 166-168
Potential roles of GB virus type C and human immunodeficiency virus coinfection on host immunomodulation
Idris Abdullahi Nasir1, Abdurrahman Elfulaty Ahmad2, Amos Dangana3
1 Department of Medical Microbiology and Parasitology, College of Health Sciences, University of Ilorin, Ilorin; Department of Medical Laboratory Services, University of Abuja Teaching Hospital, Gwagwalada, Abuja, Nigeria
2 Department of Medicine, Immunology Unit, Ahmadu Bello University, Zaria, Nigeria
3 Department of Medical Laboratory Services, University of Abuja Teaching Hospital, Gwagwalada, Abuja, Nigeria
|Date of Web Publication||25-Oct-2018|
Mr. Idris Abdullahi Nasir
Department of Medical Laboratory Services, University of Abuja Teaching Hospital, Gwagwalada, FCT Abuja
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Nasir IA, Ahmad AE, Dangana A. Potential roles of GB virus type C and human immunodeficiency virus coinfection on host immunomodulation. J Med Soc 2018;32:166-8
|How to cite this URL:|
Nasir IA, Ahmad AE, Dangana A. Potential roles of GB virus type C and human immunodeficiency virus coinfection on host immunomodulation. J Med Soc [serial online] 2018 [cited 2019 Apr 20];32:166-8. Available from: http://www.jmedsoc.org/text.asp?2018/32/2/166/244136
Human immunodeficiency virus (HIV) infection is mostly associated with coinfection (s) with other pathogens such as Mycobacterium tuberculosis and Hepatitis B virus, which usually lead to accelerated progression to acquired immunodeficiency syndrome (AIDS). However, certain coinfections may play beneficial roles. Infections with certain flaviviruses, such as West Nile virus, dengue virus, and most importantly, GB virus (GBV) type C, have been reported to reduce HIV viral load from in vivo studies. Several studies strongly support the ideology that persistent coinfection with some nonpathogenic viruses could prolong the survival of HIV-infected persons. This is because coinfected individuals show higher CD4+ cell counts, lower HIV RNA viral loads, and may live three times longer than clinically matched HIV mono-infected persons.
The experiment that led to the discovery of GBV was conducted in 1995 at Abbott Laboratories where infections of tamarins with two transmissible agents known as GBV-A and GBV-B were isolated. These infections were initially isolated from the serum of a surgeon with name initial GB who had non-A and non-B hepatitis. Using molecular technique and human sera containing antibodies recognizing GBV-A and/or GBV-B recombinant proteins, a novel virus was identified and tentatively named GBV-C.
GBV-C is the most closely related to hepatitis C virus and has been shown to share about 30% amino acid homology with HCV and more than 95% homology with hepatitis G virus., However, GBV-C replicates in lymphocytes but not hepatocytes. GBV-C has a global distribution and is transmitted horizontally, parenterally, and through vertical transmission. Thus, coinfection with viruses with a similar mode of transmission HIV is common. Till date, no human disease has been attributed to GBV-C.
Epidemiologically, the prevalence of GBV-C is about 50% for individuals at high risk for other parenterally transmitted viruses such as HCV, HIV, or Hepatitis B virus., Generally, immunocompetent individuals eliminate GBV-C within early years of infection. However, in some persons, GBV-C persistence may exist for decades. Clearance of GBV-C is often associated with the development of antibodies against the E2 region of the virus. GBV-C E2 antibodies are 2–6 times more prevalent than GBV-C RNA and may protect against reinfection. However, in some cases, GBV-C clearance does not result in the development of E2 antibodies.,
Several mechanisms have been postulated to explain the beneficial effects of GBV-C in HIV-infected persons. These include direct inhibition of HIV-1 entry modification of antiviral cytokine production, modification of HIV co-receptor expression, T-cell activation, and Fas-mediated apoptosis. Consequently, understanding of these mechanisms may open novel therapeutic strategies for HIV/AIDS. For instance, a study showed that GBV-C coinfection alters the cytokine profile in HIV infection. By preserving and boosting the innate antiviral response to infection with HIV, GBV-C may stabilize the antiviral response to HIV. Since HIV entry into host cells depends on its interaction with CD4 cells and chemokine co-receptors (CCR5 or CXCR4 or both). In peripheral blood mononuclear cells' culture, HIV and GBV-C coinfection resulted in inhibition of HIV replication, as measured by the detection of p24 antigen in culture supernatants.
Early reports that raised interest on GBV-C in HIV disease were those conducted in 1998. The first reported that GBV-C coinfection had no adverse effect on the clinical course of HIV in a cohort of 41 HIV-infected Japanese persons. GBV-C viremia was detected in 27% of patients. Surprisingly, HIV patients coinfected with GBV-C showed lower mean HIV RNA levels. Moreover, there was no significant trend toward slower progression to AIDS and improved survival. Subsequently, another study that involved 197 HIV-infected German patients reported 17% GBV-C viremic participants. They demonstrated that higher baseline CD4 cell counts, slower progression to AIDS, and improved survival rates were associated with GBV-C and HIV coinfection. These observations attracted much interest and were supported further by subsequent studies. One of such was the inverse relationship between GBV-C and HIV viral load reported by Björkman et al. This suggests an inhibition of HIV replication by GBV-C. In patients on antiretroviral therapy (ART), it was found that median GBV-C RNA levels increased, whereas this decreased upon stopping ART and subsequent resumption of HIV viral load. This depicts an inverse correlation between HIV and GBV-C dynamics. Other studies demonstrated an improved initial virological response to ART, a reduced risk of HIV viral rebound after initiating ART, and better quality of life in those with HIV and GBV-C coinfection., Despite these, there have also been some controversies regarding the beneficial roles of GBV-C on the course of HIV infection, as some studies have failed to confirm positive impact of GBV-C and HIV coinfection.
In a study, 157 HIV-positive patients early after HIV seroconversion and 23% patients coinfected with GBV-C showed no impact on the clinico-immunological outcomes of HIV-1 infection. In another study where 27% of HIV patients had detectable GBV-C viremia, coinfection did not predict HIV outcome, and there was no association between GBV-C viremia with progression of AIDS, and the overall HIV mortality was reported. Both studies included participants whom were ART naive, possibly explaining the reason for the contrasting results.
The mechanisms that explain the beneficial roles of GBV-C coinfection on HIV disease progression has raised considerable interest in this flavivirus and thus warrant further study to hopefully discover novel therapeutic options for combating HIV infection in the nearest future.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Bagasra O, Bagasra AU, Sheraz M, Pace DG. Potential utility of GB virus type C as a preventive vaccine for HIV-1. Expert Rev Vaccines 2012;11:335-47.
Sheraz M, Kanak M, Hasan M, Bhattarai R, Mahalingam K, Sealey LA, et al.
Use of flaviviral genetic fragments as a potential prevention strategy for HIV-1 silencing. J Infect Dev Ctries 2016;10:870-9.
Schwarze-Zander C, Blackard JT, Rockstroh JK. Role of GB virus C in modulating HIV disease. Expert Rev Anti Infect Ther 2012;10:563-72.
Leary TP, Muerhoff AS, Simons JN, Pilot-Matias TJ, Erker JC, Chalmers ML,et al
. Sequence and genomic organization of GBV-C: A novel member of the flaviviridae associated with human non-A-E hepatitis. J Med Virol 1996;48:60-7.
Stark K, Bienzle U, Hess G, Engel AM, Hegenscheid B, Schluter V, et al.
Detection of the hepatitis G virus genome among injecting drug users, homosexual and bisexual men, and blood donors. J Infect Dis 1996;174:1320-3.
Dawson GJ, Schlauder GG, Pilot-Matias TJ, Thiele D, Leary TP, Murphy P, et al.
Prevalence studies of GB virus-C infection using reverse transcriptase-polymerase chain reaction. J Med Virol 1996;50:97-103.
Kleinman S. Hepatitis G virus biology, epidemiology, and clinical manifestations: Implications for blood safety. Transfus Med Rev 2001;15:201-12.
Björkman P, Flamholc L, Widell A. GB virus C and survival in persons with HIV infection. N Engl J Med 2004;350:2617-8.
Nunnari G, Nigro L, Palermo F, Attanasio M, Berger A, Doerr HW, et al.
Slower progression of HIV-1 infection in persons with GB virus C co-infection correlates with an intact T-helper 1 cytokine profile. Ann Intern Med 2003;139:26-30.
Xiang J, McLinden JH, Chang Q, Jordan EL, Stapleton JT. Characterization of a peptide domain within the GB virus C NS5A phosphoprotein that inhibits HIV replication. PLoS One 2008;3:e2580.
Toyoda H, Fukuda Y, Hayakawa T, Takamatsu J, Saito H. Effect of GB virus C/hepatitis G virus coinfection on the course of HIV infection in hemophilia patients in japan. J Acquir Immune Defic Syndr Hum Retrovirol 1998;17:209-13.
Heringlake S, Ockenga J, Tillmann HL, Trautwein C, Meissner D, Stoll M, et al.
GB virus C/hepatitis G virus infection: A favorable prognostic factor in human immunodeficiency virus-infected patients? J Infect Dis 1998;177:1723-6.
Björkman P, Flamholc L, Molnegren V, Marshall A, Güner N, Widell A, et al.
Enhanced and resumed GB virus C replication in HIV-1-infected individuals receiving HAART. AIDS 2007;21:1641-3.
Rodriguez B, Woolley I, Lederman MM, Zdunek D, Hess G, Valdez H, et al.
Effect of GB virus C coinfection on response to antiretroviral treatment in human immunodeficiency virus-infected patients. J Infect Dis 2003;187:504-7.
Mosam A, Sathar MA, Dawood H, Cassol E, Esterhuizen TM, Coovadia HM, et al.
Effect of GB virus C co-infection on response to generic HAART in African patients with HIV-1 clade C infection. AIDS 2007;21:1377-9.
Björkman P, Flamholc L, Nauclér A, Molnegren V, Wallmark E, Widell A, et al.
GB virus C during the natural course of HIV-1 infection: Viremia at diagnosis does not predict mortality. AIDS 2004;18:877-86.