Seronegative Hepatitis C Virus Infection in a Child Infected via Mother-to-Child Transmission

Larouche, Ariane; Gaëtan, Geneviève; El-Bilali, Nabil; Quesnel-Vallières, Mathieu; Martin, Steven R.; Álvarez, Fernando; Shoukry, Naglaa H.; Soudeyns, Hugo

doi:10.1128/jcm.00622-12

Cited by 14 publications

(19 citation statements)

References 35 publications

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“…Indeed, children TVC80 and TV386, who exhibited low MHSI values between the latest time point and the one directly preceding it, also showed significant neutralizing Ig responses at around 1 year of age, whereas late serum from child TVC56, with a paired MHSI of 0.889 between 210 and 385 days of age, neutralized none of the variants tested. The apparent failure to develop HCV-specific neutralizing Ig responses in child TVC56 could also be compatible with immune tolerance to HCV brought about by in utero exposure to viral antigens (19,43,44,49). Testing of neutralizing activity in sera from women and children also revealed that sera from women infected with HCV alone exhibited no neutralizing activity and that no such activity appeared to have been transferred to their children, a mechanism that should have contributed to protecting the fetus from microbial infections (50).…”

Section: Figmentioning

confidence: 88%

“…In the case of HIV-1, it is well established that only one variant is transmitted from mother to child in the large majority of cases (11)(12)(13)(14). Studies that analyzed quasispecies profile based on the sequence of hypervariable region 1 (HVR1) of the HCV E2 envelope protein in HCVinfected newborns and infants suggested that vertical transmission of HCV may also involve a restricted number of viral variants (15)(16)(17)(18)(19). However, this issue has neither been comprehensively investigated nor resolved.…”

Section: Importancementioning

confidence: 99%

“…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%

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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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Section: Figmentioning

confidence: 88%

Section: Importancementioning

confidence: 99%

Section: Figmentioning

confidence: 99%

See 1 more Smart Citation

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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“…While results from other groups support these observations [131], other studies reported a gradual diversification of HCV quasispecies independent of serum ALT levels [115]. Protracted evolution of the variant profile was also observed in children who acquired both HCV and HIV-1 via MTCT [132,133], in HCV-infected children suffering from X-linked agammaglobulinemia [134], and in an anecdotal case of persistently seronegative, perinatally-acquired HCV infection [135]. In adults, chronic HCV infection may lead to cirrhosis and hepatocellular carcinoma in 10 to 20% of patients [136].…”

Section: Pathogenesis Of Hepatitis C In Childhoodmentioning

confidence: 90%

Pathogenesis of Hepatitis C During Pregnancy and Childhood

Campion

Larouche

Fauteux‐Daniel

et al. 2012

Viruses

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The worldwide prevalence of HCV infection is between 1% and 8% in pregnant women and between 0.05% and 5% in children. Yet the pathogenesis of hepatitis C during pregnancy and in the neonatal period remains poorly understood. Mother-to-child transmission (MTCT), a leading cause of pediatric HCV infection, takes place at a rate of <10%. Factors that increase the risk of MTCT include high maternal HCV viral load and coinfection with HIV-1 but, intriguingly, not breastfeeding and mode of delivery. Pharmacological prevention of MTCT is not possible at the present time because both pegylated interferon alfa and ribavirin are contraindicated for use in pregnancy and during the neonatal period. However, this may change with the recent introduction of direct acting antiviral agents. This review summarizes what is currently known about HCV infection during pregnancy and childhood. Particular emphasis is placed on how pregnancy-associated immune modulation may influence the progression of HCV disease and impact MTCT, and on the differential evolution of perinatally acquired HCV infection in children. Taken together, these developments provide insights into the pathogenesis of hepatitis C and may inform strategies to prevent the transmission of HCV from mother to child.

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“…In chronic cases, where evolution took place over a long period, the HCV population may be replaced by a new community (Gismondi et al 2013). Nevertheless, constraints are sometimes observed in the HVR1 region, limiting its molecular evolution over time and maintaining the viral population relatively unaltered, even during longer periods of time (Gismondi et al 2009;Larouche et al 2012).…”

Section: Discussionmentioning

confidence: 99%

Multiregion deep sequencing of hepatitis C virus: An improved approach for genetic relatedness studies

Rossi

Escobar‐Gutiérrez

Rahal

2016

Infection, Genetics and Evolution

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Hepatitis C virus (HCV) is a major public health problem that affects more than 180 million people worldwide. Identification of HCV transmission networks is of critical importance for disease control. HCV related cases are often difficult to identify due to the characteristic long incubation period and lack of symptoms during the acute phase of the disease, making it challenging to link related cases to a common source of infection. Additionally, HCV transmission chains are difficult to trace back since viral variants from epidemiologically linked cases are genetically related but rarely identical. Genetic relatedness studies primarily rely on information obtained from the rapidly evolving HCV hypervariable region 1 (HVR1). However, in some instances, the rapid divergence of this region can lead to loss of genetic links between related isolates, which represents an important challenge for outbreak investigations and genetic relatedness studies. Sequencing of multiple and longer sub-genomic regions has been proposed as an alternative to overcome the limitations imposed by the rapid molecular evolution of the HCV HVR1. Additionally, conventional molecular approaches required to characterize the HCV intra-host genetic variation are laborious, time-consuming, and expensive while providing limited information about the composition of the viral population. Next generation sequencing (NGS) approaches enormously facilitate the characterization of the HCV intra-host population by detecting rare variants at much lower frequencies. Thus, NGS approaches using multiple sub-genomic regions should improve the characterization of the HCV intra-host population. Here, we explore the usefulness of multiregion sequencing using a NGS platform for genetic relatedness studies among HCV cases.

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Seronegative Hepatitis C Virus Infection in a Child Infected via Mother-to-Child Transmission

Cited by 14 publications

References 35 publications

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

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

Pathogenesis of Hepatitis C During Pregnancy and Childhood

Multiregion deep sequencing of hepatitis C virus: An improved approach for genetic relatedness studies

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