Abstract
Despite common incidence of GB virus C/Hepatitis G virus (GBV-C/HGV) and Torque Teno Virus (TTV) co-infections in subjects with Hepatitis C virus (HCV) infection, pathogenic role of these co-infections in HCV infected subjects has not been clear since studies have mostly been based on liver enzyme profile yielding variable results. Pro-inflammatory cytokines that participate in host immune response against viruses are generated as a consequence of triggering of related genes by Nuclear Factor Kappa B (NF-kB) that is a member of transcription family. Study of three pro-inflammatory cytokines e.g. interleukin 1 beta (IL-1β), Interleukin-6 (IL-6), interleukin-8 (IL-8) in a group of multi-transfused thalassemic subjects in relation to positivity for HCV, HGV and TTV infections showed elevated levels of these cytokines in serum as well as in supernatant of peripheral blood mononuclear cell (PBMCs) cultures in HCV-GBV-C/HGV co-infected subgroup compared to HCV mono-infected subgroup (p <0.05 for comparison of all three cytokines) while HCV-TTV co-infected subgroup showed lowering of these levels compared to HCV mono-infected subgroup (p <0.05 for comparison of all three cytokines). Levels of p65 component of NF-kB i.e.NF-kB p65 in nuclear extracts of lipopolysaccharide stimulated PBMCs correlated positively with the levels of pro-inflammatory cytokines in serum as well as that in supernatants of PBMC cultures in both HCV- GBV-C/HGV co-infected and HCV-TTV co-infected subgroups (p values ranging from <0.001 to 0.004). Levels of NF-kB p65 in nuclear extracts and levels of pro-inflammatory cytokines in serum as well as in supernatants of PBMC culture did not show any alteration compared to thalassemic subjects with HGV or TTV infections alone and healthy non-transfused subjects. Based on the inhibitory role of TTV on activation of NF-kB in TTV-HCV co-infected cases observed in the present study and the reported contribution of NF-kB towards development of hepatocellular carcinoma (HCC) due to establishment of chronicity, it may be worth evaluating if TTV or any component of TTV can be utilized as therapeutic vaccine against development of HCC in HCV infected subjects.
Highlights
Co-infections of GB Virus C/ Hepatitis G virus (GBV-C/HGV) and Torque Teno virus (TTV) have been frequently reported to be associated with Hepatitis C virus (HCV) infection in multi-transfused individuals (Prati et al, 1999; Sehgal & Sharma 2002; Sampietro et al, 1997; Alavi et al, 2011)
Level of NF-κB p65 were estimated in nuclear extracts of cultured peripheral blood mononuclear cells (PBMCs) as a measure of activation of pro-inflammatory genes to find out their correlation with the levels of pro-inflammatory cytokines secreted by PBMC culture
Out of 200 samples tested for HIV, Hepatitis B virus (HBV), HCV, TTV and HGV infection by molecular analysis, no sample was positive for HIV infection while only two samples were positive for HBV (HBsAg positive) alone that were excluded from analysis for the purpose of the present study
Summary
Co-infections of GB Virus C/ Hepatitis G virus (GBV-C/HGV) and Torque Teno virus (TTV) have been frequently reported to be associated with Hepatitis C virus (HCV) infection in multi-transfused individuals (Prati et al, 1999; Sehgal & Sharma 2002; Sampietro et al, 1997; Alavi et al, 2011). Falasca et al, 2006) Activation of these pro-inflammatory cytokines is triggered by Nuclear factor kappa beta (NF-κB), a transcription factor present in the cytoplasm of all eukaryotic cells. A component of NF-κB with molecular weight of 65 kd (NF-κB p65) is translocated into the nucleus in response to various stimuli including viral infections triggering activation of the genes for pro-inflammatory cytokines (Tripathi & Aggarwal 2006; Baldwin, 1996). A study was carried out in HCV infected children of beta thalassemia major co-infected with GBV-C/HGV or TTV to measure levels of IL-1β, IL-6 and TNF-α in serum as well as in culture of peripheral blood mononuclear cells (PBMCs). Level of NF-κB p65 were estimated in nuclear extracts of cultured PBMCs as a measure of activation of pro-inflammatory genes to find out their correlation with the levels of pro-inflammatory cytokines secreted by PBMC culture
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