Hepatitis C virus molecular evolution: Transmission, disease progression and antiviral therapy

Hepatitis C virus (HCV) infection represents an important public health problem worldwide. Reduction of HCV morbidity and mortality is a current challenge owned to several viral and host factors. Virus molecular evolution plays an important role in HCV transmission, disease progression and therapy outcome. The high degree of genetic heterogeneity characteristic of HCV is a key element for the rapid adaptation of the intrahost viral population to different selection pressures (e.g., host immune responses and antiviral therapy). HCV molecular evolution is shaped by different mechanisms including a high mutation rate, genetic bottlenecks, genetic drift, recombination, temporal variations and compartmentalization. These evolutionary processes constantly rearrange the composition of the HCV intrahost population in a staging manner. Remarkable advances in the understanding of the molecular mechanism controlling HCV replication have facilitated the development of a plethora of direct-acting antiviral agents against HCV. As a result, superior sustained viral responses have been attained. The rapidly evolving field of anti-HCV therapy is expected to broad its landscape even further with newer, more potent antivirals, bringing us one step closer to the interferon-free era.Fil: Preciado, María Victoria. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños ; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Valva, Pamela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños ; ArgentinaFil: Escobar Gutierrez, Alejandro. Instituto de Diagnóstico y Referencia Epidemiológicos; MéxicoFil: Rahal, Paula. Universidade Estadual Paulista Julio de Mesquita Filho; BrasilFil: Ruiz Tovar, Karina. Instituto de Diagnóstico y Referencia Epidemiológicos; MéxicoFil: Yamasaki, Lilian. Universidade Estadual Paulista Julio de Mesquita Filho; BrasilFil: Vazquez Chacon, Carlos. Instituto de Diagnóstico y Referencia Epidemiológicos; MéxicoFil: Martinez Guarneros, Armando. Instituto de Diagnóstico y Referencia Epidemiológicos; MéxicoFil: Carpio Pedroza, Juan Carlos. Instituto de Diagnóstico y Referencia Epidemiológicos; MéxicoFil: Fonseca Coronado, Salvador. Universidad Nacional Autónoma de México; MéxicoFil: Cruz Rivera, Mayra. Universidad Nacional Autónoma de México; Méxic

Vertical transmission of hepatitis C virus: A tale of multiple outcomes

Globally, hepatitis C virus (HCV) infection affects approximately 130 million people and 3 million new infections occur annually. HCV is also recognized as an important cause of chronic liver disease in children. The absence of proofreading properties of the HCV RNA polymerase leads to a highly error prone replication process, allowing HCV to escape host immune response. The adaptive nature of HCV evolution dictates the outcome of the disease in many ways. Here, we investigated the molecular evolution of HCV in three unrelated children who acquired chronic HCV infection as a result of mother-to-child transmission, two of whom were also coinfected with HIV-1. The persistence of discrete HCV variants and their population structure were assessed using median joining network and Bayesian approaches. While patterns of viral evolution clearly differed between subjects, immune system dysfunction related to HIV coinfection or persistent HCV seronegativity stand as potential mechanisms to explain the lack of molecular evolution observed in these three cases. In contrast, treatment of HCV infection with PegIFN, which did not lead to sustained virologic responses in all 3 cases, was not associated with commensurate variations in the complexity of the variant spectrum. Finally, the differences in the degree of divergence suggest that the mode of transmission of the virus was not the main factor driving viral evolution. (C) 2013 Elsevier B. V. All rights reserved