Association between active GB virus-C (hepatitis G) infection and HIV-1 disease in Uganda.

Although not linked to a disease, GB virus-C viraemia has been associated with an improved prognosis in HIV-1-co-infected individuals. Most studies have been conducted on men (men who have sex with men or injection drug users) infected with HIV-1 subtype B, whereas here we report on both male and female subjects from rural Uganda, predominantly infected via the heterosexual route with HIV-1 subtypes A and D. In a longitudinal study of 272 participants, 47 were GBV-C positive and 181 negative, as determined by reverse transcription-polymerase chain reaction, in both of two plasma samples taken a median of 5.0 years apart. The remainder either acquired (25) or cleared (19) infection. Multilevel regression analyses and Cox survival analyses revealed that participants chronically infected with GBV-C had a slower decline in CD4(+) T cells (P<0.001) and increased survival time (P=0.041) compared with GBV-C RNA-negative, HIV-positive adults. We show that the association between active GBV-C co-infection and improved survival of HIV-1-infected adults is not restricted to HIV subtype B, but is also observed in both males and females infected with HIV subtypes A and D.

Infections with flaviviridae.

The family of the Flaviviridae contains 3 genera: (i) the hepaciviruses, to which belongs Hepatitis C virus (HCV), (ii) the flaviviruses and (iii) the pestiviruses. Over 140 million people, more than four times the number of HIV-positive individuals, are chronically infected with the HCV. Hepatitis G virus (HGV) has not yet been assigned to a genus. The impact of this recently discovered virus is yet to be established. Infections with flaviviruses such as Yellow Fever virus (YFV), Dengue Fever virus (DENV), Japanese Encephalitis virus (JEV) and Tick-borne Encephalitis virus (TBEV) are emerging world-wide. The Pestiviruses, Bovine Viral Diarrhea virus (BVDV), Classical Swine Fever virus (CSFV) and Border Disease virus (BDV) have a serious impact on life-stock. At present, only treatment with interferon, alone or combined with ribavirin, has been approved for the treatment of HCV infections. No specific antivirals are available for the treatment of infections with Hepaci-, Flavi- or Pestiviruses. Possible targets for inhibition of the replication of Flaviviridae are the binding to, and the uptake of the virus in the cell; the internal ribosomal entry site (IRES) of Hepaci- and Pestiviruses; viral proteases; the viral RNA-dependent RNA polymerase and the viral helicase. The search for specific inhibitors of HCV replication is hindered by the absence of an efficient cell culture system for propagation of this virus. In addition, small laboratory animals, including mice, are not susceptible to HCV infection. Flaviviruses may cause infection in mice, but do so mainly following direct intracerebral inoculation. We have established a small animal model for flavivirus infections in SCID mice inoculated peripherally with the murine flavivirus Modoc.

Hepatitis C virus: clades and properties.

Hepatitis C virus (HCV) is a member of the virus family Flaviviridae. At present HCV is classified into a discrete hepacivirus genus and is represented by six clades according to genome sequencing. Each clade is further divisible into subtypes, which may prove important for the study of clinical differences and epidemiological studies. Limited homology also exists with hepatitis G/GB viruses, despite the fact that the hepatotropic nature of the latter agents remains contentious. The variability amongst the six HCV clades is less than that observed between the four serotypes of dengue, suggesting that each clade may represent a distinct virus were tests such as plaque neutralization to become available for delineating HCV isolates. The distribution worldwide varies, with Clades 1 and 2 predominating in most regions-an important consideration for the development of any vaccine. In addition, the clade distribution among cohorts may vary according to age. Point source outbreaks of HCV, for example in large numbers of women inadvertently infected with HCV-contaminated anti-D globulin, offers an opportunity to study the evolution of HCV genotypes over several decades. Parallel studies in chimpanzees have shown that the hypervariable region of E2 may play a role in HCV immunity, with quasispecies rapidly replacing the predominant subtype as immunity develops to the initiating virus strain. There is some evidence that an IFN-sensitive motif exists in the NS5 gene which may have some predictive value in determining the likely outcome of IFN treatment. A database is available for all HCV sequences, together with information about their properties and guidance for the evaluation of new isolates (http://s2as02.genes.nig.ac.jp).