Interferon resistance of hepatitis C virus genotypes 1a/1b: relationship to structural E2 gene quasispecies mutations

Hepatitis C virus [HCV] envelope glycoprotein-2 [E2] inhibits the interferon [IFN]induced, double stranded RNA activated protein kinase [PKR] via PKR eukaryotic initiation factor-2a phosphorylation homology domain [PePHD]. Present study examined the genetic variability of the PePHD in patients receiving interferon therapy. The PePHD region from HCV genotype 1a/1b infected patients receiving IFN was amplified by reverse transcriptase polymerase chain reaction [RT-PCR] and analyzed using bidirectionaly sequencing. The PePHD sequence was different in pretreatment isolates from three months treated patients. It was shown that the major PePHD quasispecies could change after three months IFN therapy and in one patient; the major PePHD quasispecies could change after six months IFN therapy. These mutations were occurred at codons 665, 666 and 667 of followed-up samples and at codons 660, 661, 666 and 670 of randomly treated patients. Some of these mutations were similar to those reported in previous studies. Other mutations were also detected in upstream and downstream regions of PePHD which may have influenced the structure, conformation and configuration of this region and thereby suppressing PePHD inhibitory properties. In conclusion our data suggested that HCV E2 PePHD may play an important role in determining the interferon response among Iranian HCV infected patients

Relevalence of hepatitis B virus genome variability in organ transplantation

Hepatitis B virus [HBV] can cause acute and chronic hepatitis in humans, with the latter possibly leading to liver cirrhosis and hepatocellular carcinoma. The clinical course of HBV infection is critically dependent on genetic and immune features of the host as well as on virological factors. In situations of immune suppression, e.g. in patients after organ transplantation with chronic HBV infection, severe progression of liver disease can occur, due to direct effects of immunosuppressive regimens on HBV's hepatotoxicity or replication and due to the selection of HBV mutants. HBV variants are commonly found in chronically infected patients because of the lack of proofreading capacity of the HBV reverse transcriptase. Examples of relevant HBV mutations include precore or basal core promoter mutants with increased replication capacity, escape mutants with alterations in the 'a-determinant' immune epitope, core gene deletions after renal transplantation, antiviral drug resistant strains and accumulation of complex HBV variants after long-term immune suppression. In this review, we present the virological background of HBV genetic variability, discuss frequent mutations observed in transplanted patients and address the effects of HBV genetic variability on the clinical outcome in solid organ transplant recipients