On hepatitis C virus evolution: the interaction between virus and host towards treatment outcome

• Published in: PloS one Vol. 8; no. 4; p. e62393
• Main Authors: Bittar, Cíntia, Jardim, Ana Carolina Gomes, Yamasaki, Lilian Hiromi Tomonari, Carareto, Claudia Márcia Aparecida, Pinho, João Renato Rebello, Lemey, Philippe, de Carvalho-Mello, Isabel Maria Vicente Guedes, Rahal, Paula
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 25-04-2013; Public Library of Science (PLoS)
• Subjects: Amino Acid Sequence; Amino acids; Analysis; Automation; Biodiversity; Biological evolution; Biological response modifiers; Biology; Care and treatment; Disease spread; Disease transmission; Etiology; Evolution; Evolution, Molecular; Evolutionary genetics; Gastroenterology; Gene sequencing; Genetic diversity; Genetic research; Genetic Variation; Genomes; Genomics; Genotype; Genotype & phenotype; Hepacivirus - genetics; Hepacivirus - metabolism; Hepacivirus - physiology; Hepatitis; Hepatitis C; Hepatitis C - therapy; Hepatitis C - virology; Hepatitis C virus; Host-Pathogen Interactions; Humans; Hypothesis testing; Immune system; Interferon; Kinases; Laboratories; Language; Medical treatment; Medicine; Molecular Sequence Data; Mutation; Patient outcomes; Patients; Population biology; Population structure; Proteins; Resists; Ribonucleic acid; RNA; RNA polymerase; RNA viruses; Science; Therapy; Treatment Outcome; Uniqueness; Viral Nonstructural Proteins - chemistry; Viral Nonstructural Proteins - metabolism; Viral proteins; Viruses; Brazil
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0062393

Hepatitis C is a disease spread throughout the world. Hepatitis C virus (HCV), the etiological agent of this disease, is a single-stranded positive RNA virus. Its genome encodes a single precursor protein that yields ten proteins after processing. NS5A, one of the non-structural viral proteins, is most associated with interferon-based therapy response, the approved treatment for hepatitis C in Brazil. HCV has a high mutation rate and therefore high variability, which may be important for evading the immune system and response to therapy. The aim of this study was to analyze the evolution of NS5A quasispecies before, during, and after treatment in patients infected with HCV genotype 3a who presented different therapy responses.
Viral RNA was extracted, cDNA was synthesized, the NS5A region was amplified and cloned, and 15 clones from each time-point were sequenced. The sequences were analyzed for evolutionary history, genetic diversity and selection.
This analysis shows that the viral population that persists after treatment for most non-responder patients is present in before-treatment samples, suggesting it is adapted to evade treatment. In contrast, the population found in before treatment samples from most end-of-treatment responder patients either are selected out or appears in low frequency after relapse, therefore changing the population structure. The exceptions illustrate the uniqueness of the evolutionary process, and therefore the treatment resistance process, in each patient.
Although evolutionary behavior throughout treatment showed that each patient presented different population dynamics unrelated to therapy outcome, it seems that the viral population from non-responders that resists the treatment already had strains that could evade therapy before it started.