Evidence that the GBV-C/hepatitis G virus is primarily a lymphotropic virus

Abstract

GB virus-C and the hepatitis G virus (GBV-C/HGV) are variants of the same positive sense RNA flavivirus, initially thought to be associated with hepatitis. The tissue tropism of GBV-C/HGV in normal subjects has not been evaluated to date using an extended tissue spectrum. Therefore, the sites of GBV-C/HGV replication were investigated in serum and twenty-three tissues collected during post-mortem examination of four apparently healthy individuals who died accidental deaths, who were infected with GBV-C/HGV. All were anti-HIV and anti-HCV negative and three out of four were HBsAg negative. Tissues were collected carefully to prevent cross contamination. A highly strand-specific RT-PCR assay was employed for the detection of either GBV-C/HGV positive strand RNA (virion) or negative strand RNA (replicative intermediary). Strand specificity of the RT-PCR assay was assessed with synthetic positive-and negative strand GBV-C/HGV RNA generated from a plasmid, using T7 and T3 RNA polymerases. The spleen and bone marrow biopsies were found to be uniformly positive for both negative-and positive strand GBV-C/HGV RNA. In addition, one cadaver was positive for both RNA strands in the kidney, and another positive for both in the liver. No negative strand RNA was detected in the following: brain, muscle, heart, thyroid, salivary gland, tonsil, lung, lymph nodes, gall bladder, pancreas, oesophagus, stomach, small bowel, large bowel, adrenal gland, gonad, aorta, skin and cartilage. This preliminary study concludes that GBV-C/HGV is a lymphotropic virus that replicates primarily in the spleen and bone marrow.

GBV-C Infection and Risk of NHL among U.S. Adults

“…GBV-C RNA is commonly detected in bone marrow and spleen tissue (10, 11), and GBV-C has been demonstrated to replicate in vitro in peripheral blood mononuclear cells, particularly B and T lymphocytes (12, 13). Chronic GBV-C infection has been associated with decreased apoptosis of T cells, impaired T cell activation and proliferation, and changes in immune responsiveness which may contribute to lymphomagenesis (14–16).…”

Comparison of GB virus C, HIV, and HCV infection markers in hemophiliacs exposed to non-inactivated or inactivated factor concentrates

“…However, as a result of several large epidemiological studies there was no evidence for the association of GBV-C infection and hepatitis (Alter et al, 1997a(Alter et al, , 1997b. Moreover, several research groups have documented GBV-C to be not hepatotropic (Laskus et al, 1997(Laskus et al, , 1998Pessoa et al, 1998) but primarily lymphotropic (Tucker et al, 2000). In vitro studies have shown that GBV-C is able to productively infect PBMC (Fogeda et al, 1999;George et al, 2003) and Xiang et al (2000) could show that in vitro transfection of primary CD4+ T lymphocytes with a full length GBV-C RNA led to active viral replication.…”

GB virus C: Insights into co-infection

“…In contrast to HCV, GBV-C does not appear to be hepatotrophic as the virus neither replicates in hepatocytes nor causes acute or chronic hepatitis (Alter, 1997;Laskus et al, 1997). In fact, GBV-C is a lymphotrophic virus that is believed to replicate primarily in the spleen and bone marrow (Tucker et al, 2000). There is also some evidence that the virus replicates in a number of different peripheral blood mononuclear cells, including CD4 positive T cells (Xiang et al, 2000).…”