Genetic variability of hepatitis C virus before and after combined therapy of interferon plus ribavirin.

PloS One
José Manuel CuevasFernando González-Candelas

Abstract

We present an analysis of the selective forces acting on two hepatitis C virus genome regions previously postulated to be involved in the viral response to combined antiviral therapy. One includes the three hypervariable regions in the envelope E2 glycoprotein, and the other encompasses the PKR binding domain and the V3 domain in the NS5A region. We used a cohort of 22 non-responder patients to combined therapy (interferon alpha-2a plus ribavirin) for which samples were obtained before initiation of therapy and after 6 or/and 12 months of treatment. A range of 25-100 clones per patient, genome region and time sample were sequenced. These were used to detect general patterns of adaptation, to identify particular adaptation mechanisms and to analyze the patterns of evolutionary change in both genome regions. These analyses failed to detect a common adaptive mechanism for the lack of response to antiviral treatment in these patients. On the contrary, a wide range of situations were observed, from patients showing no positively selected sites to others with many, and with completely different topologies in the reconstructed phylogenetic trees. Altogether, these results suggest that viral strategies to evade selection pressure from ...Continue Reading

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Citations

Sep 10, 2010·Virology Journal·Fernando González-CandelasMaria Alma Bracho
Feb 5, 2013·BMC Infectious Diseases·Ana C G JardimPaula Rahal
Feb 26, 2011·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Tohru NoguchiShuhei Nishiguchi
Jun 16, 2009·Journal of Virological Methods·Pilar Domingo-CalapRafael Sanjuán
Feb 25, 2009·Journal of Medical Virology·José M CuevasAndrés Moya
Dec 15, 2010·Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases·Xiaogang XiangJin Zhong
Oct 2, 2012·Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases·Verónica SaludesElisa Martró
Feb 27, 2020·International Journal of Molecular Sciences·Cristina Romero-López, Alfredo Berzal-Herranz

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Datasets Mentioned

BETA
AF009606

Methods Mentioned

BETA
PCR

Software Mentioned

PHYML
DnaSP
MEGA
VESPA
PAML

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