Comparison of serum and liver hepatitis C virus quasispecies in HCV-related hepatocellular carcinoma

Mitri, Marco Di; Mele, Loredana; Chen, Chiu Hua; Piccinini, Andrea; Chianese, R.; d’Errico, Angelo; Alberti, Alfredo; Pisi, E

doi:10.1016/s0168-8278(98)80115-3

Cited by 22 publications

(14 citation statements)

References 29 publications

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“…Early studies demonstrated the presence of a larger number of HCV variants in cancerous lesions than in surrounding tissues regardless of the presence of cirrhosis. 182,183 Sequencing of the NS5A region showed a higher prevalence of wildtype strains (no mutations within domain 2209-2248 compared to the prototype 1b strain) in cirrhotic patients who later developed HCC, compared with those who maintained the cirrhotic status. 184 Using a rigorous statistical approach, Sobesky et al more recently confirmed a marked compartmentalization of HCV between tumor and nontumor tissues, showing that the viral quasispecies within the tumor was more diversified and subject to a weaker selective pressure compared with that in the surrounding tissue.…”

Section: Compartmentalization Of the Hcv Quasispeciesmentioning

confidence: 99%

New Insights into the HCV Quasispecies and Compartmentalization

Farci

2011

Semin Liver Dis

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Hepatitis C virus (HCV) is a hepatotropic RNA virus with an extraordinary propensity to persist in the vast majority of infected individuals. During replication, because of the inherent infidelity of the viral RNA polymerase, each progeny RNA genome contains mutations that lead to a continuous diversification of the viral population. Consequently, HCV circulates in vivo as a quasispecies, which is a dynamic distribution of divergent but closely related genomes subjected to a continuous process of genetic variation, competition, and selection. This genomic heterogeneity confers a remarkable advantage to the viral population allowing for a rapid adaptation to a changing environment when the virus is subject to selective constraints exerted by the host, such as antiviral immunity, or external to the host, such as antiviral therapy. The large reservoir of variants provided by the quasispecies represents a great challenge for the control of HCV infection and has important biologic implications for viral persistence, host cell tropism, antiviral drug resistance, and development of an HCV vaccine. This review discusses the molecular mechanisms of HCV genetic variation and the biologic and clinical relevance of the quasispecies nature of HCV.

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Section: Compartmentalization Of the Hcv Quasispeciesmentioning

confidence: 99%

New Insights into the HCV Quasispecies and Compartmentalization

Farci

2011

Semin Liver Dis

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“…Another factor of interest is the HCV quasispecies. Differences of HCV quasispecies have been demonstrated between non-cancerous and HCC tissue [Kurosaki et al, 1995;Saito et al, 1996;De Mitri et al, 1998], which possibly related to viral biological properties such as cell tropism and virus titer.…”

Section: Introductionmentioning

confidence: 99%

Variation of hepatitis C virus load, hypervariable region 1 quasispecies and CD81 hepatocyte expression in hepatocellular carcinoma and adjacent non‐cancerous liver

Young¹,

Lin²,

Hsiao³

et al. 2002

Journal of Medical Virology

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Hepatitis C virus (HCV) infection is etiologically associated with the development of hepatocellular carcinoma (HCC) worldwide. HCV has been reported to exist and replicate in both HCC and adjacent non-cancerous liver tissue, but limited information was available on HCV viral load and quasispecies composition in HCC relative to adjacent non-cancerous hepatocytes. Previous study has also suggested CD81, a surface hepatocyte protein, as a receptor for HCV. To clarify the above, HCV-RNA and CD81-RNA titers in 20 paired hepatectomized liver and serum were quantitatively measured by chemiluminescent RT-cPCR. Hypervariable region 1 (HVR-1) variations of parallel specimens were analyzed after subcloning in 6 patients. HCV-RNA levels in serum and non-cancerous liver were markedly higher for HCV genotype 1 than genotype non-1. HCV levels were markedly higher in non-cancerous liver than in HCC (P = 0.001) in a genotype-independent manner, with a mean ratio of 56:1 for non-cancerous tissue to HCC. Both non-cancerous and HCC tissues had the same level of CD81-RNA expression, which was not linked to HCV load. HCV-RNA quantity in both HCC and non-cancerous liver correlated with the number of HVR-1 quasispecies in the tissue, and distinct HVR-1 subclones existed.

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“…C urrently available information on the molecular biology of the hepatitis C virus (HCV) in the liver has been generated mainly by studies carried out in frozen liver tissue specimens (Brambilla et al, 1998;Cabot et al, 1997;De Mitri et al, 1998;Okuda et al, 1999;Sakai et al, 1999). Recently, several authors reported that HCV-RNA sequences may also be recovered and amplified by RT-PCR from formalin-fixed, paraffin-embedded (FFPE) liver tissue (Abe et al, 1998;Akyol et al, 1992;Bresters et al, 1992;Edamato et al, 1996;el-Batanony et al, 1994;Guerrero et al, 1997), even when stored for more than 20 years (Mizuno et al, 1998;Soguero et al, 1999).…”

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confidence: 99%

Assessment of Genotype and Molecular Evolution of Hepatitis C Virus in Formalin-Fixed Paraffin-Embedded Liver Tissue from Patients With Chronic Hepatitis C Virus Infection

Soguero

Campo

Ribalta

et al. 2000

Laboratory Investigation

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SUMMARY:Drawbacks of hepatitis C virus (HCV) RNA detection in paraffin-embedded liver tissue have satisfactorily been solved by RT-PCR amplification of the 5Јnon-coding region (5ЈNCR). However, detection of this highly conserved region does not provide information on epidemiological or pathogenetic aspects of HCV infection. This study explores whether other functionally important genetic regions of HCV, such as the hypervariable region 1 (HVR-1) and the interferon sensitivity-determining region (ISDR), can be retrieved from paraffin-embedded liver specimens by RT-PCR, and whether the amplified material is suitable for further molecular analyses. RT-PCR amplification of 5ЈNCR, HVR-1, and ISDR was assessed in RNA extracted from 50 formalin-fixed, paraffin-embedded liver specimens, including 23 needle liver biopsies (11 from patients with non-A, non-B chronic hepatitis diagnosed between 1971 and 1985, 8 from subjects with normal liver histology and 4 from sequential biopsies from a patient with HCV recurrence after liver transplantation), and 27 liver explants from patients undergoing transplantation between 1988 and 1996 (16 with HCV-related cirrhosis and 11 with other disorders). The 5ЈNCR was successfully amplified in 8 of 11 (73%) non-A, non-B chronic hepatitis biopsies and in all of the specimens from patients with serological documentation of HCV infection. There were no false-positive results. HCV genotype was identified by RFLP analysis of the 5ЈNCR in the 13 cases analyzed. HVR-1 and ISDR were amplified in 24 of 28 (86%) samples, which were positive for the 5ЈNCR. Efficient amplification was inversely related to the time of storage. The evolutionary changes of HVR-1 and ISDR were successfully analyzed by direct sequencing of amplificates from the explanted liver and from the sequential liver biopsies in a patient with HCV infection recurrence after transplantation. These observations indicate that paraffin-embedded liver tissue, even when stored for more than 20 years, is appropriate for advanced studies on the molecular biology of HCV. (Lab Invest 2000, 80:851-856).

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Comparison of serum and liver hepatitis C virus quasispecies in HCV-related hepatocellular carcinoma

Cited by 22 publications

References 29 publications

New Insights into the HCV Quasispecies and Compartmentalization

New Insights into the HCV Quasispecies and Compartmentalization

Variation of hepatitis C virus load, hypervariable region 1 quasispecies and CD81 hepatocyte expression in hepatocellular carcinoma and adjacent non‐cancerous liver

Assessment of Genotype and Molecular Evolution of Hepatitis C Virus in Formalin-Fixed Paraffin-Embedded Liver Tissue from Patients With Chronic Hepatitis C Virus Infection

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