Virology

Edited by: Paul Smaglik T.P. Leary, A.S. Muerhoff, J.N. Simons, T.J. Pilot-Matias, J.C. Erker, M.L. Chalmers, G.G. Schlauder, G.J. Dawson, S.M. Desai, I.K. Mushahwar, "Sequence and genomic organization of GBV-C: A novel member of the Flaviviridae associated with human non-A-E hepatitis," Journal of Medical Virology, 48:60-7, 1996. (Cited more than 150 times since its publication in January 1996) Comments by Thomas P. Leary and Isa K. Mushahwar, Virus Discovery Group, Abbott Laboratories Inc., North Chicago, Ill. VIRAL SURPRISE: Abbott Laboratories' Thomas Leary was looking for GBV-A or GBV-B in a human sample but found GBV-C instead. UNKNOWN IMPACT: Since GBV-C rarely occurs alone, scientists will have a difficult time assessing its contribution to hepatitis, says Abbott Laboratories' Isa Mushahwar. Ten percent to 20 percent of human hepatitis cases are of unknown origin. Scientists suspected that GB virus A (GBV-A) and GB virus B (GBV-B), two viruses found only in animals (J.N. Simons et al., Nature Medicine, 1:564-9, 1995), could account for some of those cases. The authors of this paper expected to find one of those forms as they sequenced a novel hepatitis virus from a human subject; instead, they found a variant, which they named GB virus C (GBV-C). "We were very surprised when we found it," says Thomas P. Leary, a research investigator with Abbott Laboratories Inc. in North Chicago, Ill. "We were expecting to find GBV-A or GBV-B." Extending the genomic sequence and analyzing the viral polyprotein revealed how the GBV-C virus is related to, but distinct from, the other agents that cause hepatitis. An analysis by Leary's team showed that genetically, GBV-C most closely resembles GBV-A, with fewer similarities to GBV-B. The new virus also shares some genetic similarities with hepatitis C virus (HCV). Both GBV-C and HCV are transmitted through infected blood. However, Leary notes, more recent work reveals that GBV-C is a flavivirus, one of several viral strains that cause hepatitis, with a twist. When he and colleagues first sequenced the virus and compared it with similar viruses, they were unable to identify the initiating methionine residue. Leary and colleagues suspected the virus lacked the core protein encoded by other members of the Flaviviridae. Further studies have since confirmed that hunch, he notes. "They allowed us to definitively determine that the virus GBV-C did not encode a core protein." The research also drew attention clinically because the virus is transmitted via blood. "Anything that is transmitted in blood or blood products is of major concern to the public health community," Leary says. He and colleagues have developed a polymerase chain reaction-based assay to detect the virus. Researchers have since found GBV-C in thousands of patients-many times accompanying HCV (G.J. Dawson et al., Journal of Medical Virology, 50:97-103, 1996). This is not surprising, since both viruses are transmitted in the same manner. One of the key questions that remains, he adds, is whether this virus is a major cause of disease. Isa K. Mushahwar, Distinguished Research Fellow and director of virus discovery at Abbott Laboratories, warns that since few individuals are infected with GBV-C alone, researchers can't yet conclusively answer that question. However, existing data have provided some clues about the effects of the virus. "Overall, 80 [percent] to 90 percent of the patients infected with GBV-C have mild, transient, and self-limiting diseases. Most of these subclinical cases resolve with little or no known damage to liver tissue." However, Mushahwar cautions that, in the remainder of cases, the disease can be nearly as severe as HCV-an alarming fact, since patients carrying the GBV-C virus can remain asymptomatic for long periods. Researchers need a larger number of patients to draw a more solid conclusion. Mushahwar also notes the importance of studying the effects of GBV-C infection in the absence of other parenterally transmitted diseases such as HCV. Additionally, researchers could benefit the field by analyzing liver tissue from infected subjects to see if the virus multiplies there and damages the tissue in a manner similar to HCV. Since this study, more scientists have analyzed viruses molecularly, rather than in cell culture, thanks to the "triumph of molecular biology," Mushahwar declares. "Now we have the tools not only to dissect the virus but also to discover the unique mutations within these viruses."

Virology

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