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准种多样性是垂直传播丙型肝炎病毒的主要危险因素。

Quasispecies Diversity Is a Major Risk Factor for Vertical Hepatitis C Virus Transmission.

机构信息

Unité immunopathologie virale, Centre de recherche du Centre hospitalier universitaire (CHU) Sainte-Justine, Montreal, Quebec, Canada.

Department of Microbiology, Infectiology and Immunology, Faculty of Medicine, Université de Montréal, Canada.

出版信息

J Infect Dis. 2019 Feb 15;219(5):760-771. doi: 10.1093/infdis/jiy581.

Abstract

BACKGROUND

Vertical transmission is the major cause of pediatric hepatitis C virus (HCV) infection. The objective of this study was to better understand HCV pathogenesis in pregnant women and provide insights into risk factors and mechanisms involved in vertical transmission.

METHODS

Evolutionary dynamics of HCV variant spectra and HCV-specific neutralizing antibody responses were examined using high-throughput sequencing and pseudoparticle-based assays in pregnant women monoinfected with HCV (n = 17) or coinfected with HCV and human immunodeficiency virus (HIV)-1 (n = 15).

RESULTS

Overall, statistically significant associations were found between HCV quasispecies diversity, selective pressure exerted on the HCV E2 envelope protein, and neutralizing activity of maternal immunoglobulins. Women with low quasispecies diversity displayed significantly higher mean aspartate aminotransferase and alanine aminotransferase levels throughout pregnancy, but this difference was restricted to monoinfected participants. Low quasispecies diversity and inefficient neutralizing activity were also significantly associated with vertical transmission, but only in the monoinfected group.

CONCLUSIONS

These results indicate that maternal neutralizing antibody responses play a role in the prevention of vertical HCV transmission, but not in presence of HIV-1 coinfection, and suggest that the mechanism of vertical transmission may be different between monoinfected and coinfected women. These findings could inform management strategies for the prevention of vertical HCV transmission.

摘要

背景

垂直传播是小儿丙型肝炎病毒(HCV)感染的主要原因。本研究旨在更好地了解孕妇 HCV 的发病机制,并深入了解垂直传播涉及的危险因素和机制。

方法

采用高通量测序和假病毒检测方法,对 17 例 HCV 单一感染孕妇和 15 例 HCV 和人类免疫缺陷病毒(HIV)-1 混合感染孕妇进行 HCV 变异谱和 HCV 特异性中和抗体反应的演变动力学研究。

结果

总体而言,HCV 准种多样性、HCV E2 包膜蛋白所受选择压力和母体免疫球蛋白的中和活性之间存在统计学显著关联。整个孕期准种多样性低的女性丙氨酸氨基转移酶和天冬氨酸氨基转移酶水平显著升高,但这种差异仅限于 HCV 单一感染的参与者。低准种多样性和低效中和活性也与垂直传播显著相关,但仅在 HCV 单一感染组中如此。

结论

这些结果表明,母体中和抗体反应在预防垂直 HCV 传播中起作用,但在 HIV-1 混合感染时不起作用,并提示垂直传播的机制在 HCV 单一感染和混合感染的女性中可能不同。这些发现可为预防垂直 HCV 传播的管理策略提供信息。

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