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

Escobar‐Gutiérrez, Alejandro; Soudeyns, Hugo; Larouche, Ariane; Carpio-Pedroza, Juan Carlos; Martínez-Guarneros, Armando; Vazquez-Chacon, Carlos A.; Fonseca-Coronado, Salvador; Yamasaki, Lílian Hiromi Tomonari; Ruiz‐Tovar, Karina; Cruz-Rivera, Mayra

doi:10.1016/j.meegid.2013.10.005

Cited by 8 publications

(14 citation statements)

References 42 publications

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“…Again, at least two different sub-populations (2 and 3) that accounts for more than 50% of the hayplotypes observed arose in the quasispecies population and are situated in different spaces in the network by comparison with sub-population 1, which contains the master sequence (Figure 3). These results suggest a divergent virus quasispecies population that occupied large extensions of the sequence space [56].…”

Section: Discussionmentioning

confidence: 86%

Bayesian Coalescent Analysis of the Intra-Host Evolution of Hepatitis C Virus: Memory Genomes and Clinical Implications

Recarey¹,

Cristina²

2014

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Genetic variability plays a key role in the biology and medical treatment of RNA viruses. As an RNA virus, Hepatitis C virus (HCV) replicate as complex distributions of closely related genomes termed viral quasispecies. The behavior of the evolving HCV quasispecies population is influenced by the ensemble of mutants that compose the viral population. One such influence is the presence of minority subpopulations, termed memory genomes, in the mutant spectra. Biologically relevant mutants have been previously observed to be present as memory genomes in RNA viral populations. For that reason, an in-depth analysis of HCV quasispecies populations is crucial for our understanding viral evolution, drug resistance and therapy outcome. Recently developed next-generation sequencing (NGS) platforms make it possible to investigate viral quasispecies at much greater detail. In order to gain insight into these matters, we have performed a Bayesian coalescent analysis of hypervariable region 1 (HVR1) sequences of a HCV quasispecies population circulating in a chronic patient, recently obtained by ultra-deep sequencing. The results of these studies revealed a mean rate of evolution of HCV HVR1 of the intra-host quasispecies population of 4.80 × 10 −2 amino acid substitutions/site/year. A sharp and rapid diversification of the HCV quasispecies isolated from the patient in three different sub-populations was observed. The most abundant sequence in the quasispecies population was not found to be the center of a tight and complex network around this sequence, suggesting that the quasispecies population as a whole efficiently explore a wide sequence space. Co-evolution of relevant amino acid sites had been identified in the HVR1. This speaks of the possible roll of these residues in HVR1 to allow the virus to shift between combinations of residues to escape the immune system while retaining its structure and functions. The results of these studies highlight the importance of minority genomes in HCV population history and evolution, the mutant clouds as reservoirs of phenotypic and genetic variants for virus adaptability, as well as the roll of the mutant spectra to overcome selective con-*

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Section: Discussionmentioning

confidence: 86%

Bayesian Coalescent Analysis of the Intra-Host Evolution of Hepatitis C Virus: Memory Genomes and Clinical Implications

Recarey¹,

Cristina²

2014

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“…It might also have significant implications regarding HCV pathogenesis, as the presence of circulating HCV in the fetus during this period could lead to long-term tolerance to HCV antigens and loss of pathogen-specific immune competence (43,44). Indeed, midgestation in utero infection was hypothesized to represent a possible contributing factor to the long-term persistent HCV-seronegative status observed in a child who acquired HCV by vertical transmission (19,45). Finally, examination of variant population structure in the TVC55-TVC56 and the TVC79-TVC80 mother-child pairs also provided compelling but circumstantial evidence (i.e., maternal variants emerging from child clusters) that transmission of HCV from the fetus to the mother could also have taken place during pregnancy, similar to what was recently hypothesized to occur in maternofetal infection by Zika virus (46).…”

Section: Figmentioning

confidence: 99%

Vertical Transmission of Hepatitis C Virus: Variable Transmission Bottleneck and Evidence of Midgestation In Utero Infection

Fauteux‐Daniel

Larouche

Calderon

et al. 2017

J Virol

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Hepatitis C virus (HCV) can be transmitted from mother to child during pregnancy and childbirth. However, the timing and precise biological mechanisms that are involved in this process are incompletely understood, as are the determinants that influence transmission of particular HCV variants. Here we report results of a longitudinal assessment of HCV quasispecies diversity and composition in 5 cases of vertical HCV transmission, including 3 women coinfected with human immunodeficiency virus type 1 (HIV-1). The population structure of HCV variant spectra based on E2 envelope gene sequences (nucleotide positions 1491 to 1787), including hypervariable regions 1 and 2, was characterized using next-generation sequencing and median-joining network analysis. Compatible with a loose transmission bottleneck, larger numbers of shared HCV variants were observed in the presence of maternal coinfection. Coalescent Bayesian Markov chain Monte Carlo simulations revealed median times of transmission between 24.9 weeks and 36.1 weeks of gestation, with some confidence intervals ranging into the 1st trimester, considerably earlier than previously thought. Using recombinant autologous HCV pseudoparticles, differences were uncovered in HCV-specific antibody responses between coinfected mothers and mothers infected with HCV alone, in whom generalized absence of neutralization was observed. Finally, shifts in HCV quasispecies composition were seen in children around 1 year of age, compatible with the disappearance of passively transferred maternal immunoglobulins and/or the development of HCVspecific humoral immunity. Taken together, these results provide insights into the timing, dynamics, and biologic mechanisms involved in vertical HCV transmission and inform preventative strategies.IMPORTANCE Although it is well established that hepatitis C virus (HCV) can be transmitted from mother to child, the manner and the moment at which transmission operates have been the subject of conjecture. By carrying out a detailed examination of viral sequences, we showed that transmission could take place comparatively early in pregnancy. In addition, we showed that when the mother also carried human immunodeficiency virus type 1 (HIV-1), many more HCV variants were shared between her and her child, suggesting that the mechanism and/or the route of transmission of HCV differed in the presence of coinfection with HIV-1. These results

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“…Untranslated 5 'and 3' ends contain important regions for viral replication, region nearby 5' end contains information coding for the structural proteins in the regions C, E1, E2 and NS1. The remainder of the genome codes for the nonstructural proteins is encoded by the regions NS2, NS3, NS4 and NS5 (20). The virus must interact with hepatocyte membrane receptors, then endocytosed and released into cytoplasm, there, the RNA is translated directly and peptidases present in the endoplasmic reticulum of the host cell cleave the 5'-end, causing proteins C, E1, E2 and NS1 nonstructural proteins to be released, which are cleaved by the action of viral proteases (21,22), this cycle allows a wide range of targets.…”

Section: Virologymentioning

confidence: 99%

Expectations of Treatment of Hepatitis C in Children

Figueroa¹,

Gamboa-Cardeña²,

García‐Mena³

et al. 2016

West Indian Med J

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Background: HCV infection in children differs from infection in adult through transmission paths, spontaneous viral clearance rate, and fibrosis progression duration of chronic infection. It is estimated that the rate of children with chronic hepatitis C will develop cirrhosis is less than 2%, however there are reports of children requiring liver transplantation. Objective: Was to present a general overview of the current treatments for HCV infection in children. Material and method: Databases such as PubMed, MEDLINE and Scopus were used as information sources to identify and analyzed the current information about the treatment for HCV infection in children. Results: In children the most commonly used drugs are pegylated alpha interferon in combination with ribavirin, both drugs are given in combination therapy in children over 3 years of age with detectable HCV RNA levels. The side effects reported are similar like to adults, including leukopenia, anemia, weight loss (determined by anorexia, nausea, and abdominal pain), changes in behavior, depression, suicidal ideation, thyroid disorders, and transient slowing of the growth rate. Recently, it has been approved that the other drugs with direct antiviral activity (DAAs), the protease inhibitors NS3/4, Boceprevir and Telaprevir were introduced into clinical practice in adults, only Boceprevir was tested and not approved for use in children, (Clinical Trials gob No P07614), adverse effects were reported in 37.5% of participants and included nausea, fatigue, malaise, increased systolic pressure, increased liver enzymes.

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

Cited by 8 publications

References 42 publications

Bayesian Coalescent Analysis of the Intra-Host Evolution of Hepatitis C Virus: Memory Genomes and Clinical Implications

Bayesian Coalescent Analysis of the Intra-Host Evolution of Hepatitis C Virus: Memory Genomes and Clinical Implications

Vertical Transmission of Hepatitis C Virus: Variable Transmission Bottleneck and Evidence of Midgestation In Utero Infection

Expectations of Treatment of Hepatitis C in Children

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