Evidence of intratypic recombination in natural populations of hepatitis C virus.

Hepatitis C virus (HCV) has high genomic variability and, since its discovery, at least six different types and an increasing number of subtypes have been reported. Genotype 1 is the most prevalent genotype found in South America. In the present study, three different genomic regions (5'UTR, core and NS5B) of four HCV strains isolated from Peruvian patients were sequenced in order to investigate the congruence of HCV genotyping for these three genomic regions. Phylogenetic analysis using 5'UTR-core sequences found strain PE22 to be related to subtype 1b. However, the same analysis using the NS5B region found it to be related to subtype 1a. To test the possibility of genetic recombination, phylogenetic studies were carried out, revealing that a crossover event had taken place in the NS5B protein. We discuss the consequences of this observation on HCV genotype classification, laboratory diagnosis and treatment of HCV infection.

[1]  M. Georgescu,et al.  High diversity of poliovirus strains isolated from the central nervous system from patients with vaccine-associated paralytic poliomyelitis , 1994, Journal of virology.

[2]  S. Guillot,et al.  Natural Genetic Exchanges between Vaccine and Wild Poliovirus Strains in Humans , 2000, Journal of Virology.

[3]  R. Colina,et al.  Evidence of increasing diversification of hepatitis C viruses. , 1999, The Journal of general virology.

[4]  K. Lole,et al.  Full-Length Human Immunodeficiency Virus Type 1 Genomes from Subtype C-Infected Seroconverters in India, with Evidence of Intersubtype Recombination , 1999, Journal of Virology.

[5]  R. Rico-Hesse,et al.  Dengue Virus Structural Differences That Correlate with Pathogenesis , 1999, Journal of Virology.

[6]  T. Gojobori,et al.  Intragenic recombinations in rotaviruses , 1998, FEBS letters.

[7]  A. Sönnerborg,et al.  Discrepancy of hepatitis C virus genotypes as determined by phylogenetic analysis of partial NS5 and core sequences , 1996, Journal of medical virology.

[8]  Andrew Rambaut,et al.  Seq-Gen: an application for the Monte Carlo simulation of DNA sequence evolution along phylogenetic trees , 1997, Comput. Appl. Biosci..

[9]  M. Mizokami,et al.  New hepatitis C virus (HCV) genotyping system that allows for identification of HCV genotypes 1a, 1b, 2a, 2b, 3a, 3b, 4, 5a, and 6a , 1997, Journal of clinical microbiology.

[10]  A. Heath,et al.  Isolation of an Intertypic Poliovirus Capsid Recombinant from a Child with Vaccine-Associated Paralytic Poliomyelitis , 2002, Journal of Virology.

[11]  J. Lau,et al.  Evaluation of a novel serotyping system for hepatitis C virus: strong correlation with standard genotyping methodologies , 1995, Journal of clinical microbiology.

[12]  E. Holmes,et al.  Identification of genotypes of hepatitis C virus by sequence comparisons in the core, E1 and NS-5 regions. , 1994, The Journal of general virology.

[13]  E. Domingo,et al.  RNA virus mutations and fitness for survival. , 1997, Annual review of microbiology.

[14]  E. Holmes,et al.  Analysis of a new hepatitis C virus type and its phylogenetic relationship to existing variants. , 1992, The Journal of general virology.

[15]  D. Casane,et al.  Evidence of recombination in natural populations of hepatitis A virus. , 2003, Virology.

[16]  E. Holmes,et al.  Widespread intra-serotype recombination in natural populations of dengue virus. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[17]  P. Laurent-Puig,et al.  Hepatitis C virus genotyping by means of 5'-UR/core line probe assays and molecular analysis of untypeable samples. , 1995, Virus research.

[18]  M. Pallansch,et al.  Outbreak of Poliomyelitis in Hispaniola Associated with Circulating Type 1 Vaccine-Derived Poliovirus , 2002, Science.

[19]  E. Holmes,et al.  Evolutionary aspects of recombination in RNA viruses. , 1999, The Journal of general virology.

[20]  P. Simmonds,et al.  Review: Molecular epidemiology of hepatitis C virus , 1997, Journal of gastroenterology and hepatology.

[21]  R. Charrel,et al.  Evidence for recombination in natural populations of dengue virus type 1 based on the analysis of complete genome sequences. , 2001, The Journal of general virology.

[22]  R. Colina,et al.  Analysis of genetic heterogeneity of hepatitis C viruses in Central America reveals a novel genetic lineage , 2002, Archives of Virology.

[23]  I. Uhnoo,et al.  Confirmation of Nosocomial Transmission of Hepatitis C Virus by Phylogenetic Analysis of the NS5-B Region , 1998, Journal of Clinical Microbiology.

[24]  S. McWilliam,et al.  Comparison of a dengue-2 virus and its candidate vaccine derivative: Sequence relationships with the flaviviruses and other viruses☆ , 1992, Virology.

[25]  M. Orlich,et al.  RNA Recombination between Persisting Pestivirus and a Vaccine Strain: Generation of Cytopathogenic Virus and Induction of Lethal Disease , 2001, Journal of Virology.

[26]  H J Alter,et al.  Recovery, Persistence, and Sequelae in Hepatitis C Virus Infection: A Perspective on Long-Term Outcome , 2000, Seminars in liver disease.

[27]  L. Stuyver,et al.  Typing of hepatitis C virus isolates and characterization of new subtypes using a line probe assay. , 1993, The Journal of general virology.

[28]  A. Widell,et al.  Mixed Infection with Two Types of Hepatitis C Virus Is Probably a Rare Event , 2000, Infection.

[29]  R. H.J.MULLE THE RELATION OF RECOMBINATION TO MUTATIONAL ADVANCE , 2002 .

[30]  E. Holmes,et al.  The extent of homologous recombination in members of the genus Flavivirus. , 2003, The Journal of general virology.

[31]  R. Rico-Hesse,et al.  Molecular evolution and distribution of dengue viruses type 1 and 2 in nature. , 1990, Virology.

[32]  E. Holmes,et al.  Homologous recombination in GB virus C/hepatitis G virus. , 2001, Molecular biology and evolution.

[33]  Duane J. Gubler,et al.  Dengue and Dengue Hemorrhagic Fever , 1998, Clinical Microbiology Reviews.

[34]  L. Kinnunen,et al.  Evidence of Recombination among Enteroviruses , 1999, Journal of Virology.

[35]  P. Simmonds,et al.  Sequence analysis of hepatitis C virus variants producing discrepant results with two different genotyping assays , 1997, Journal of medical virology.

[36]  E. Holmes,et al.  Phylogenetic evidence for recombination in dengue virus. , 1999, Molecular biology and evolution.

[37]  Sudhir Kumar,et al.  MEGA: Molecular Evolutionary Genetics Analysis software for microcomputers , 1994, Comput. Appl. Biosci..

[38]  S. Kwok,et al.  Avoiding false positives with PCR , 1989, Nature.

[39]  K. Strimmer,et al.  A novel exploratory method for visual recombination detection , 2003, Genome Biology.

[40]  M. Yanagi,et al.  Transcripts of a chimeric cDNA clone of hepatitis C virus genotype 1b are infectious in vivo. , 1998, Virology.

[41]  Olga Kalinina,et al.  A Natural Intergenotypic Recombinant of Hepatitis C Virus Identified in St. Petersburg , 2002, Journal of Virology.

[42]  P. Simmonds,et al.  Viral heterogeneity of the hepatitis C virus. , 1999, Journal of hepatology.

[43]  J. Thompson,et al.  CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. , 1994, Nucleic acids research.

[44]  W. An,et al.  Human Immunodeficiency Virus Type 1 Genetic Recombination Is More Frequent Than That of Moloney Murine Leukemia Virus despite Similar Template Switching Rates , 2003, Journal of Virology.

[45]  T. Monath,et al.  Dengue: the risk to developed and developing countries. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[46]  M. Sakamoto,et al.  Characterization of the genomic sequence of type V (or 3a) hepatitis C virus isolates and PCR primers for specific detection. , 1993, The Journal of general virology.

[47]  R. Rico-Hesse,et al.  Genetic variation of Japanese encephalitis virus in nature. , 1990, The Journal of general virology.

[48]  M. Thomson,et al.  Genetic recombination and its role in the development of the HIV‐1 pandemic , 2002, AIDS.

[49]  R. Colina,et al.  Diversification of hepatitis C viruses in South America reveals a novel genetic lineage , 2001, Archives of Virology.

[50]  E. Holmes,et al.  Molecular epidemiology of dengue type 2 virus in Venezuela: evidence for in situ virus evolution and recombination. , 2001, The Journal of general virology.

[51]  P. Simmonds,et al.  Molecular Epidemiology of Hepatitis C Virus , 2002 .

[52]  P. Simmonds,et al.  Mapping of serotype-specific, immunodominant epitopes in the NS-4 region of hepatitis C virus (HCV): use of type-specific peptides to serologically differentiate infections with HCV types 1, 2, and 3 , 1993, Journal of clinical microbiology.

[53]  M. Peeters,et al.  High genetic diversity of HIV-1 strains in Chad, West Central Africa. , 2003, Journal of acquired immune deficiency syndromes.