Evolution of naturally occurring 5'non-coding region variants of Hepatitis C virus in human populations of the South American region

Moratorio, Gonzalo; Martínez, Mariela; Gutiérrez, María Lucía Lahoz; González, Katiuska; Colina, Rodney; Tort, Luis Fernando López; López, Lilia; Recarey, Ricardo; Schijman, Alejandro G.; Moreno, Pilar; García-Aguirre, Laura; Manascero, Aura R; Cristina, Juan

doi:10.1186/1743-422x-4-79

Cited by 8 publications

(9 citation statements)

References 37 publications

(38 reference statements)

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“…Alignment of sequence (region that confers sub domain IIIb of 5 0 UTR region) showed that contact point between [145][146][147][148][149][150][151][152][153][154][155][156] are highly conserved among all strains isolated from patient showed SVR and did not showed SVR to antiviral treatment [Hazari et al, 2005]. In agreement with Moratorio et al [Moratorio et al, 2007] a rare nucleotide substitution is observed at G 243A, though did not disrupt stem loop III folding and suggesting that maintaining of the structure of the internal ribosomal entry site is prerequisite for survival of quasispecies in host cell (Thelu et al, 2004). In addition C-T and C-A substitution at position 202 among patients achieved SVR and non-SVR needs further study.…”

Section: Discussionsupporting

confidence: 62%

Optimum predictors of therapeutic outcome in HCV patients in Pakistan

Aziz

Raza

Irfan

2015

Journal of Medical Virology

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Hepatitis C virus (HCV) constitutes a major public health issue in Pakistan. Interferon α and ribavirin is used widely in routine practice in HCV infected patients in Pakistan.Treatment prediction is an important tool in therapy management. The present study aims to evaluate trends of predictive variables of treatment outcome in patients with different genotypes. The analysis comprised of 921 patients infected with different HCV genotypes. All the patients received IFN α-2b combined with ribavirin for 24 weeks. Overall, 60.2% patients achieved Sustained virologic response (SVR). In females sustained virologic response (SVR) was higher in age group <40 years (77.2%) than ≥40-50 years (60%) but in male SVR was almost equal in both age groups. We also found higher SVR with low pretreatment viral load (72.4%, P < 0.0001). Sustained Virologic Response in genotype 3a was 63.1%, 3b was 55%, 1a was 36.3% and 1b was 35% 3a +3b was 55.0% and 1a+3a was 42.9%. According to multivariable logistic regression analysis age < 40 years (2.0; 95%CI, 1.49-2.84; P = 0.0001), low pretreatment RNA level<800,000 IU/ml (4.0; 95%CI, 2.64-6.17; P = 0.0001), early virologic response at week 12 (12.3; 95%CI, 8.18-18.58; P < 0.0001) and non-fatty liver (2.5; 95%CI, 3.6-6.2; P = 0.005) showed significance for SVR. Nucleotide substitution in 5'UTR before treatment failed to show any characteristic pattern that has correlation with sustained response. Subtype 3a showed 95% presence among patients with age <40 years while older patients showed 79.9%.

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Section: Discussionsupporting

confidence: 62%

Optimum predictors of therapeutic outcome in HCV patients in Pakistan

Aziz

Raza

Irfan

2015

Journal of Medical Virology

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“…NS5B is an extremely preferred region for HCV subtyping, but it is not always accurately amplified because of primer-target mismatch to highly variable nucleotide region of NS5B ( Baclig et al, 2010 , Sandres-Saune et al, 2003 ). Although, 5′ UTR is the most conserved part of the virus genome, however; with minor variants, it expresses quasispecies distribution in the infected populations ( Moratorio et al, 2007 ), as shown in Table 3, 8% mixed subtypes were identified in HCV Saudi isolates in the current study. The reasonable justification of this phenomenon might be the existence of randomly occurring mutations distributed within 5′ UTR gene due to the error-prone nature of HCV RNA-dependent RNA polymerase during viral replication ( Moratorio et al, 2007 ).…”

Section: Discussionmentioning

confidence: 63%

“…Although, 5′ UTR is the most conserved part of the virus genome, however; with minor variants, it expresses quasispecies distribution in the infected populations ( Moratorio et al, 2007 ), as shown in Table 3, 8% mixed subtypes were identified in HCV Saudi isolates in the current study. The reasonable justification of this phenomenon might be the existence of randomly occurring mutations distributed within 5′ UTR gene due to the error-prone nature of HCV RNA-dependent RNA polymerase during viral replication ( Moratorio et al, 2007 ). In silico predicted RNA secondary structure of IRES (internal ribosome entry site) stem-loops of 5′ UTR explored that some mutations in IRES might affect IRES structure to confer a survival advantage or disadvantage to mutated HCV genome in the form of quasispecies during HCV replication- ( Moratorio et al, 2007 ).…”

Section: Discussionmentioning

confidence: 63%

“…The 5′ UTR is highly conserved (92%−98%) as compared to other HCV genome regions, mostly suited for amplification methods, and contains specific sequence motifs for HCV GTs/subtypes identification ( Baclig et al, 2010 ). Many diagnostic laboratories and most commercially available HCV typing assays target 5′ UTR due to higher genotype-based assay sensitiveness ( Moratorio et al, 2007 ). However, mounting evidences suggested that direct sequencing of 5′ UTR did not identify all existing HCV GT 1 subtypes in 20% infected cases ( Baclig et al, 2010 ).…”

Section: Discussionmentioning

confidence: 99%

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Virological surveillance, molecular phylogeny, and evolutionary dynamics of hepatitis C virus subtypes 1a and 4a isolates in patients from Saudi Arabia

Almalki

Shahid

Abdalla

et al. 2021

Saudi Journal of Biological Sciences

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Hepatitis C virus (HCV) subtypes are pre-requisite to predict endemicity, epidemiology, clinical pathogenesis, diagnosis, and treatment of chronic hepatitis C infection. HCV genotypes 4 and 1 are the most prevalent in Saudi Arabia, however; less consensus data exist on circulating HCV subtypes in infected individuals. This study was aimed to demonstrate the virological surveillance, phylogenetic analysis, and evolutionary relationship of HCV genotypes 4 and 1 subtypes in the Saudi population with the rest of the world. Fifty-five clinical specimens from different parts of the country were analyzed based on 5′ untranslated region (5′ UTR) amplification, direct sequencing, and for molecular evolutionary genetic analysis. Pair-wise comparison and multiple sequence alignment were performed to determine the nucleotide conservation, nucleotide variation, and positional mutations within the sequenced isolates. The evolutionary relationship of sequenced HCV isolates with referenced HCV strains from the rest of the world was established by computing pairwise genetic distances and generating phylogenetic trees. Twelve new sequences were submitted to GenBank, NCBI database. The results revealed that HCV subtype 4a is more prevalent preceded by 1a in the Saudi population. Molecular phylogeny predicts the descendants’ relationship of subtype 4a isolates very close to Egyptian prototype HCV strains, while 1a isolates were homogeneous and clustering to the European and North American genetic lineages. The implications of this study highlight the importance of HCV subtyping as an indispensable tool to monitor the distribution of viral strains, to determine the risk factors of infection prevalence, and to investigate clinical differences of treatment outcomes among intergenotypic and intragenotypic isolates in the treated population.

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“…This situation is in contrast with the high prevalence rates and genetic diversity found for this virus in Africa and South Eastern Asia, which might be associated to the origin of this virus [8] . No autochthonous HCV genotype has been described in the region, except for some South American lineages of G1 [10] which probably emerged during their evolution in the New World. Changes in hepatitis C virus (HCV) genotype distribution with time have been reported in several countries.…”

Section: Introductionmentioning

confidence: 99%

Genetic History of Hepatitis C Virus in Venezuela: High Diversity and Long Time of Evolution of HCV Genotype 2

et al. 2010

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BackgroundThe subtype diversity of the hepatitis C virus (HCV) genotypes is unknown in Venezuela.Methodology/Principal FindingsPartial sequencing of the NS5B region was performed in 310 isolates circulating in patients from 1995 to 2007. In the samples collected between 2005 and 2007, HCV genotype 1 (G1) was the most common genotype (63%), composed as expected of mainly G1a and G1b. G2 was the second most common genotype (33%), being G2a almost absent and G2j the most frequent subtype. Sequence analysis of the core region confirmed the subtype assignment performed within the NS5b region in 63 isolates. The complete genome sequence of G2j was obtained. G2j has been described in France, Canada and Burkina Fasso, but it was not found in Martinique, where several subtypes of G2 circulate in the general population. Bayesian coalescence analysis indicated a most recent common ancestor (MRCA) of G2j around 1785, before the introduction of G1b (1869) and G1a (1922). While HCV G1a and G1b experienced a growth reduction since 1990, coincident with the time when blood testing was implemented in Venezuela, HCV G2j did not seem to reach growth equilibrium during this period.Conclusions/SignificanceAssuming the introduction of G2j from Africa during the slave trade, the high frequency of G2j found in Venezuela could suggest: 1- the introduction of African ethnic groups different from the ones introduced to Martinique or 2- the occurrence of a founder effect. This study represents an in-depth analysis of the subtype diversity of HCV in Venezuela, which is still unexplored in the Americas and deserves further studies.

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Evolution of naturally occurring 5'non-coding region variants of Hepatitis C virus in human populations of the South American region

Cited by 8 publications

References 37 publications

Optimum predictors of therapeutic outcome in HCV patients in Pakistan

Optimum predictors of therapeutic outcome in HCV patients in Pakistan

Virological surveillance, molecular phylogeny, and evolutionary dynamics of hepatitis C virus subtypes 1a and 4a isolates in patients from Saudi Arabia

Genetic History of Hepatitis C Virus in Venezuela: High Diversity and Long Time of Evolution of HCV Genotype 2

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