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Cross-genotype immunity to Hepatitis C Virus
Randomized clinical trial of inerferon, ribavirin, and amantadine versus interferon, ribavirin and a placebo in chronic Hep C patients
Reactive oxygen species and suppression of Hep C replication
GB Virus and HIV co-infection: the effects on CD4 count
Spread of Hepatitis C Virus among IV drug users infected with HIV shows little regional clustering
Check out these 2003 and 2004 primary article updates to aspects about various flaviviridae!
Studies have shown that immunity might be possible to induce in humans in chimpanzees to decrease the incidence of chronic hepatitis C virus. This study shows that chimpanzees that recovered from genotype 1 HCV infection were protected from infection of other genotypes that were up to 30% genetically different from the parental strain. Genotypes 4; 2 and 3 mixture; and 1-4 together were tested. In all cases the level of viremia was significantly decreased from the primary infection. The genotypes must have common epitopes that were conserved during evolution of the virus. The strains used to test the reaction of the animal after primary infections were also tested on controls. These controls showed typical infections that were seen in the experimental chimpanzees’ primary infections. “Protective immunity was often associated with an early increase in gamma interferon transcripts in the liver and increase in intrahepatic transcripts of Mig, a T-cell chemokine that is a gamma interferon response gene.” Cross-genotype immunity was shown to induce an immune response after a primary infection that had beneficial effects on subsequent re-infection with different genotypes of the Hepatitis C virus.
Lanford et al. (2004) Cross-genotype Immunity to Hepatitis C Virus. Journal of Virology 78(3):1575-1581.
The efficacy of the triple therapy of interferon alfa, ribavirin, and amantadine was compared to standard therapy of interferon alfa and ribavirin in patients with chronic Hepatitis C. The trial was a prospective, randomized, double blind placebo controlled study. 85 patients received the three-dose regimen and 86 patients received the standard and placebo regimen. An HCV-PCR test was done 24 weeks after treatment stopped to determine efficacy. 32.9% of the three-dose group and 38.4% of the placebo group were HCV RNA free at testing (p=.03). Sustained viral appearance was noted in 24.7% of the 3-dose group and 27.9% of the placebo group. Poor response rates were seen in cirrhotics, African Americans, genotype 1 and higher viral load patients. Amantadine did not induce any adverse side effects. The response rate to 3 and 2-dose therapy was similar or better in the 2 dose patients leading the authors to conclude that amantadine does not play a role in HCV treatment.
Thuluvath et al. (2004) Randomized double blind, placebo controlled trial of interferon, ribavirin, and amantadine versus interferon, ribavirin, and placebo in treatment naïve patients with chronic hepatitis C. International Journal of Gastroenterology and Hepatology 53: 130-135.
Hepatitis C virus employs RNA dependent RNA polymerase to replicate and uses and internal ribosomal entry site (IRES) to translate proteins. Increased concentrations of reactive oxygen species (ROS) are usually seen in HCV infection but the effect on replication was unknown. A bicistronic subgenomic RNA replicon and genomic RNA were used to study the effect of ROS on replication in hepatoma cells. The cells were treated with peroxide at levels that did not induce apoptosis and there were significant decreases of HCV RNA levels. The cells were treated with peroxide at levels that did not induce apoptosis and there were significant decreases of HCV RNA levels. The decrease was partially reversed with an antioxidant N-acetylcystein. ROS was found to disable active replication processes by reducing the amounts of NS3 and NS5A in the part of the cell where replication complexes were. ROS can quickly disable HCV replication in human hepatoma cells.
Choi et al. (2004) Reactive Oxygen Species Suppress Hepatitis C Virus RNA Replication in Human Hepatoma Cells. Hepatology 39(1): 81-89
This study noted that it had been observed that GB virus C may have a positive effect on HIV infection by slowing the progression to AIDS and increasing survival time once AIDS has commenced. A few studies have even indicated an association between GB virus and HIV infection and increased CD4 counts. A study was performed by Muerhoff et al. where GB virus subtypes were investigated in coinfected HIV and GBV infected patients. 35 patients were tested and 33 had GB virus type C. Two of these patients had genotype 1, 12 with type 2a and 19 with type 2b. Clinical information for 25 of these patients was available (1 with genotype 1, 9 with genotype 2a, and 15 with genotype 2b). CD4 counts were lowered in patients with genotype 2a (310+/- 136) than patients with genotype 2b (430+/-199) with p=.054.
Muerhoff et al. (2003) GB Virus C Genotype Determination in GB Virus-C/HIV Co-infected Individuals. Journal of Medical Virology (70): 141-149.
The spread of HCV among HIV/HCV IV drug users was studied. A phylogenetic analysis showed significant sequence variation of HCV within each of the 7 European countries surveyed. There was no clear phylogenetic clustering by region. The subtypes found with the highest incidence were 1a and 3a, followed by genotype 4, which is found in the majority of populations studied. The fewer evolutionary differences within subtype 4b mean that the subtype may be a newer addition to the European population. There is a great mixing and exchanged of HCV between European populations, more spread out and less clustered than HIV infections.
Van Asten et al. (2004) Spread of Hepatitis C Virus Among European Injection Drug Users Infected with HIV: A Phylogenic Analysis. Journal of Infectious Diseases 189: 292-302