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Analysis of hepatitis C virus core encoding sequences in chronically infected patients reveals mutability, predominance, genetic history and potential impact on therapy of Cuban genotype 1b isolates.
Eur Rev Med Pharmacol Sci. 2011 Nov; 15(11):1320-7.ER

Abstract

BACKGROUND AND OBJECTIVES

Hepatitis C virus (HCV) genotypes are relevant to epidemiological questions, vaccine development, and clinical management of chronic HCV infection. In the present work, we aimed at investigating HCV genotype, variability and genetic history of HCV isolates in Cuba from a sample of chronically infected patients.

MATERIAL AND METHODS

A prospective study, involving 73 Cuban anti-HCV positive patients, was carried out. RT-PCR and phylogenetic analysis was employed to determine HCV genotypes. Divergence dates and demographic parameters in a Bayesian coalescent framework were estimated, as implemented in BEAST v1.4.8.

RESULTS

HCV RNA was undetectable in 15 patients that received antiviral therapy. All HCV RNA positive patients, 58, were infected with genotype 1, three of them with subtype 1a and 55 with subtype 1b. The analysis of the DNA sequence coding for a core fragment, spanning nt positions 435-816 (relative to strain H77), revealed high percent (96.7% +/- 0.8%) nucleotide identity within Cuban HCV subtype 1b sequences. However, 56.7% and 20% of 30 analyzed individuals had changes in the core region in a six-month interval, at the nucleotide and amino acid level, respectively. Mutations involving aa changes were mainly found in the region encompassed between aa 70 and 106 of the core protein, with only one isolate showing a point mutation at position 43. Interestingly, some of the observed changes seem to be reversions and might in fact contribute to reducing the variability of this region. The estimated date for the most recent common ancestor of HCV genotype 1b Cuban isolates is 1969 (CI, 1953 to 1977).

DISCUSSION

Analysis of HCV core encoding sequences from chronic patients reveals mutability of genotype 1b isolates in Cuba, which seem to be predominant and rapidly multiplied during the eighty decade of last century, and might limit the benefits obtained from current antiviral therapy.

Authors+Show Affiliations

Centro de Ingeniería Genética y Biotecnología, Havana, Cuba.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22195367

Citation

González-Horta, E E., et al. "Analysis of Hepatitis C Virus Core Encoding Sequences in Chronically Infected Patients Reveals Mutability, Predominance, Genetic History and Potential Impact On Therapy of Cuban Genotype 1b Isolates." European Review for Medical and Pharmacological Sciences, vol. 15, no. 11, 2011, pp. 1320-7.
González-Horta EE, Marante J, Amador-Cañizares Y, et al. Analysis of hepatitis C virus core encoding sequences in chronically infected patients reveals mutability, predominance, genetic history and potential impact on therapy of Cuban genotype 1b isolates. Eur Rev Med Pharmacol Sci. 2011;15(11):1320-7.
González-Horta, E. E., Marante, J., Amador-Cañizares, Y., Alvarez-Lajonchere, L., Guerra, I., Martínez-Donato, G., & Dueñas-Carrera, S. (2011). Analysis of hepatitis C virus core encoding sequences in chronically infected patients reveals mutability, predominance, genetic history and potential impact on therapy of Cuban genotype 1b isolates. European Review for Medical and Pharmacological Sciences, 15(11), 1320-7.
González-Horta EE, et al. Analysis of Hepatitis C Virus Core Encoding Sequences in Chronically Infected Patients Reveals Mutability, Predominance, Genetic History and Potential Impact On Therapy of Cuban Genotype 1b Isolates. Eur Rev Med Pharmacol Sci. 2011;15(11):1320-7. PubMed PMID: 22195367.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Analysis of hepatitis C virus core encoding sequences in chronically infected patients reveals mutability, predominance, genetic history and potential impact on therapy of Cuban genotype 1b isolates. AU - González-Horta,E E, AU - Marante,J, AU - Amador-Cañizares,Y, AU - Alvarez-Lajonchere,L, AU - Guerra,I, AU - Martínez-Donato,G, AU - Dueñas-Carrera,S, PY - 2011/12/27/entrez PY - 2011/12/27/pubmed PY - 2012/1/18/medline SP - 1320 EP - 7 JF - European review for medical and pharmacological sciences JO - Eur Rev Med Pharmacol Sci VL - 15 IS - 11 N2 - BACKGROUND AND OBJECTIVES: Hepatitis C virus (HCV) genotypes are relevant to epidemiological questions, vaccine development, and clinical management of chronic HCV infection. In the present work, we aimed at investigating HCV genotype, variability and genetic history of HCV isolates in Cuba from a sample of chronically infected patients. MATERIAL AND METHODS: A prospective study, involving 73 Cuban anti-HCV positive patients, was carried out. RT-PCR and phylogenetic analysis was employed to determine HCV genotypes. Divergence dates and demographic parameters in a Bayesian coalescent framework were estimated, as implemented in BEAST v1.4.8. RESULTS: HCV RNA was undetectable in 15 patients that received antiviral therapy. All HCV RNA positive patients, 58, were infected with genotype 1, three of them with subtype 1a and 55 with subtype 1b. The analysis of the DNA sequence coding for a core fragment, spanning nt positions 435-816 (relative to strain H77), revealed high percent (96.7% +/- 0.8%) nucleotide identity within Cuban HCV subtype 1b sequences. However, 56.7% and 20% of 30 analyzed individuals had changes in the core region in a six-month interval, at the nucleotide and amino acid level, respectively. Mutations involving aa changes were mainly found in the region encompassed between aa 70 and 106 of the core protein, with only one isolate showing a point mutation at position 43. Interestingly, some of the observed changes seem to be reversions and might in fact contribute to reducing the variability of this region. The estimated date for the most recent common ancestor of HCV genotype 1b Cuban isolates is 1969 (CI, 1953 to 1977). DISCUSSION: Analysis of HCV core encoding sequences from chronic patients reveals mutability of genotype 1b isolates in Cuba, which seem to be predominant and rapidly multiplied during the eighty decade of last century, and might limit the benefits obtained from current antiviral therapy. SN - 1128-3602 UR - https://www.unboundmedicine.com/medline/citation/22195367/Analysis_of_hepatitis_C_virus_core_encoding_sequences_in_chronically_infected_patients_reveals_mutability_predominance_genetic_history_and_potential_impact_on_therapy_of_Cuban_genotype_1b_isolates_ L2 - http://www.diseaseinfosearch.org/result/3332 DB - PRIME DP - Unbound Medicine ER -