GB virus type C infection modulates T-cell activation independently of HIV-1 viral load

Maidana-Giret, Maria Teresa; Silva, Tania; Sauer, Mariana M.; Tomiyama, Helena; Levi, José Eduardo; Bassichetto, Kátia Cristina; Nishiya, Anna S.; Diaz, Ricardo Sobhie; Sabino, Ester C.; Palácios, Ricardo; Kallas, Esper G.

doi:10.1097/qad.0b013e32832d7a11

Cited by 62 publications

(94 citation statements)

References 45 publications

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“…The application of this assay has shown its importance as a parameter for the evaluation of factors influencing the outcome of HIV/AIDS disease 14 .…”

Section: Discussionmentioning

confidence: 99%

Evaluation of GBV-C / HVG viremia in HIV-infected women

Silva

Rodrigues

Campos

et al. 2012

Rev. Inst. Med. trop. S. Paulo

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SUMMARYThe present study aimed at standardizing a real-time quantitative polymerase chain reaction assay to evaluate the presence of GBV-C/HGV RNA. A "TaqMan" assay using primers and probe derived from the 5′ NCR region was developed and validated. Two hundred and fifty-three plasma samples from HIV-infected women were tested for GBV-C viremia and antibody against the envelope protein 2. GBV-C RNA was detected in 22.5% of the patients whereas the antibody was identified in 25.3% of the cohort. Detection of viral RNA and of antibodies was mutually exclusive. Viral loads showed a mean of 1,777 arbitrary units / mL, being 1.1 and 13,625 arbitrary units / mL respectively the lowest and highest values measured. We conclude that the real-time quantitative polymerase chain reaction method developed is appropriate for the investigation of GBV-C RNA since it was shown to be highly specific and sensitive, as well as requiring few steps, preventing contamination and providing additional information as to the relative viremia of carriers, a parameter that must be included in studies evaluating the co-factors influencing the clinical outcome of HIV/AIDS.

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“…The application of this assay has shown its importance as a parameter for the evaluation of factors influencing the outcome of HIV/AIDS disease 14 .…”

Section: Discussionmentioning

confidence: 99%

Evaluation of GBV-C / HVG viremia in HIV-infected women

Silva

Rodrigues

Campos

et al. 2012

Rev. Inst. Med. trop. S. Paulo

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“…HPgV RNA was present in all 14 study subjects' PBMCs, and in highly purified populations of T-and Blymphocytes (.98 % purity), consistent with previous studies (George et al, 2006;Ruiz et al, 2010 Although HPgV replicates efficiently in humans, with mean serum viral loads typically .1610 7 genome equivalents ml 21 , replication is inefficient in vitro and the production of virus by lymphocytes maintained in culture ex vivo is reduced following T-cell activation (George et al, 2003;Rydze et al, 2012). Consistent with an interaction between HPgV and cell activation, several clinical studies observed a reduction in T-cell activation and proliferation markers in HIV-infected subjects with HPgV co-infection compared with HIV-mono-infected subjects (Bhattarai et al, 2012a;Maidana-Giret et al, 2009;Rydze et al, 2012;Stapleton et al, 2012b). Further evidence consistent with HPgV reducing inflammation comes from a recent report which found that HPgV infection was associated with reduced mortality in individuals infected with ebolavirus (Lauck et al, 2015).…”

Section: Hpgv Infects Diverse Haematopoietic Cell Types In Vitromentioning

confidence: 98%

“…macrophage inflammatory protein (MIP)-1a, MIP-1b, RANTES (CCR5) and stromal-derived factor-1 (CXCR4) (Xiang et al, 2004), in chronic HPgV viraemic subjects compared with those without HPgV infection. Additionally, the relationship between HPgV infection and reduced immune activation (Bhattarai et al, 2012a;Maidana-Giret et al, 2009) suggests that this virus has anti-inflammatory effects that may be generally beneficial to humans. In contrast, this subtle reduction in immune function may contribute to the observed association between HPgV and non-Hodgkin's lymphoma by reducing immune surveillance mechanisms (Chang et al, 2014; Civardi et al, 1998;De Renzo et al, 2002;Ellenrieder et al, 1998;Giannoulis et al, 2004; Keresztes et al, 2003; Krajden et al, 2010; Michaelis et al, 2003;Nakamura et al, 1997).…”

Section: Hpgv: An Ancient and Successful Human Virusmentioning

confidence: 99%

Tropism of human pegivirus (formerly known as GB virus C/hepatitis G virus) and host immunomodulation: insights into a highly successful viral infection

Chivero

Stapleton

2015

Journal of General Virology

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Human pegivirus (HPgV; originally called GB virus C/hepatitis G virus) is an RNA virus within the genus Pegivirus of the family Flaviviridae that commonly causes persistent infection. Worldwide, 750 million people are actively infected (viraemic) and an estimated 0.75-1.5 billion people have evidence of prior HPgV infection. No causal association between HPgV and disease has been identified; however, several studies described a beneficial relationship between persistent HPgV infection and survival in individuals infected with human immunodeficiency virus. The beneficial effect appeared to be related to a reduction in host immune activation. HPgV replicates well in vivo (mean plasma viral loads typically .1¾10 7 genome copies ml -1 ); however, the virus grows poorly in vitro and systems to study this virus are limited. Consequently, mechanisms of viral persistence and host immune modulation remain poorly characterized, and the primary permissive cell type (s) has not yet been identified. HPgV RNA is found in liver, spleen, bone marrow and PBMCs, including Tand B-lymphocytes, NK-cells, and monocytes, although the mechanism of cell-to-cell transmission is unclear. HPgV RNA is also present in serum microvesicles with properties of exosomes. These microvesicles are able to transmit viral RNA to PBMCs in vitro, resulting in productive infection. This review summarizes existing data on HPgV cellular tropism and the effect of HPgV on immune activation in various PBMCs, and discusses how this may influence viral persistence. We conclude that an increased understanding of HPgV replication and immune modulation may provide insights into persistent RNA viral infection of humans. IntroductionHuman pegivirus (HPgV) is an RNA virus within the Pegivirus A species and family Flaviviridae (Adams et al., 2013;Stapleton et al., 2012a). The virus was originally called hepatitis G virus (HGV)/GB virus type C (GBV-C). The letters 'GB' represented the initials of a surgeon with acute hepatitis whose sera caused hepatitis in marmosets (Deinhardt et al., 1967). Subsequent studies found that this virus did not cause hepatitis and there was no direct evidence that the surgeon ('G. B.') was infected with HPgV. Thus, the virus (HGV/GBV-C), along with several related primate and bat viruses (GBV-A, GBV-C czp , GBV-D), was assigned to a new genus (Pegivirus) and renamed as HPgV (Adams et al., 2013;Stapleton et al., 2012a). HPgV has a 9.4 kb positive-sense ssRNA genome that is organized similarly to hepatitis C virus (HCV) (Fig. 1). HPgV and HCV are unusual amongst RNA viruses in that they commonly cause persistent infection in immune-competent humans.Although HPgV is not as efficient at establishing persistent infection as HCV, an estimated 25 % of infections persist and the other 75 % clear viraemia within 2 years of infection (Gutierrez et al., 1997;Tanaka et al., 1998a). The prevalence of HPgV viraemia in cross-sectional serum surveys of healthy blood donors in developed countries is between 1 and 5 %, whilst up to 20 % of blood donors in ...

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“…If GBV-C infection attenuates EBOV pathogenesis, it is possible that this occurs through modulation of the host immune response. In the context of HIV infection, GBV-C has been associated with a reduced production of proinflammatory cytokines and a reduction in T-cell activation in vivo and in vitro (34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44). Conversely, robust production of proinflammatory cytokines and lymphocyte activation followed by massive T-cell death are thought to play a major role in EBOV pathogenesis and have been associated with poor clinical outcome in retrospective studies (21)(22)(23)(24)(25)(26)(27).…”

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confidence: 99%

GB Virus C Coinfections in West African Ebola Patients

Lauck

Bailey

Andersen

et al. 2015

J Virol

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In 49 patients with known Ebola virus disease outcomes during the ongoing outbreak in Sierra Leone, 13 were coinfected with the immunomodulatory pegivirus GB virus C (GBV-C). Fifty-three percent of these GBV-C ؉ patients survived; in contrast, only 22% of GBV-C ؊ patients survived. Both survival and GBV-C status were associated with age, with older patients having lower survival rates and intermediate-age patients (21 to 45 years) having the highest rate of GBV-C infection. Understanding the separate and combined effects of GBV-C and age on Ebola virus survival may lead to new treatment and prevention strategies, perhaps through age-related pathways of immune activation.

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GB virus type C infection modulates T-cell activation independently of HIV-1 viral load

Abstract: The association between GBV-C replication and lower T-cell activation may be a key mechanism involved in the protection conferred by this virus against HIV-1 disease progression to immunodeficiency in HIV-1-infected patients.

Cited by 62 publications

References 45 publications

Evaluation of GBV-C / HVG viremia in HIV-infected women

Evaluation of GBV-C / HVG viremia in HIV-infected women

Tropism of human pegivirus (formerly known as GB virus C/hepatitis G virus) and host immunomodulation: insights into a highly successful viral infection

GB Virus C Coinfections in West African Ebola Patients

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