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[疱疹病毒在女性泌尿生殖道疾病和不孕症发生发展中的作用]

[The role of herpesviruses in development of diseases of the urogenital tract and infertility in women].

作者信息

Kushch A A, Kisteneva L B, Klimova R R, Cheshik S G

机构信息

Ivanovsky Institute of Virology of FSBI «National Research Centre of Epidemiology and Microbiology named after honorary academician N.F. Gamaleya» of the Ministry of Health of Russia.

出版信息

Vopr Virusol. 2021 Jan 7;65(6):317-325. doi: 10.36233/0507-4088-2020-65-6-2.

Abstract

This review presents the data on the spreading of all known human herpesviruses (НHVs) in female urogenital tract. According to the WHO almost 500 million people worldwide suffer from genital infection caused by НHVs. НHVs were detected in various inflammatory diseases of female upper and lower genital tract (vaginitis and cervicitis), in extrauterine pregnancy (in fallopian tubes), in infertility (cervical channel, endometrium and ovaries). Herpes simplex virus 1 (HSV‑1) was identified for the first time in oocytes after failed in vitro fertilization (IVF). НHVs produce negative effect on the entire reproductive process from conception to childbirth. It was established that HSV, cytomegalovirus (CMV) and human herpesvirus 6 (HHV-6) markedly increase the risk of spontaneous abortion, preterm birth and stillbirth. Intrauterine НHV infection is a major cause of congenital malformations. Data on humoral and cell immunity in genital herpesvirus infections (НHVI) are also reviewed. Intravaginal HSV‑2 infection changes cell composition of vaginal mucosa, i.e., together with cells mobilized from the blood, protective role is performed by resident memory T‑cells (TRM), natural killer cells (NK‑cells) and regulatory T‑cells (Treg) whose function consists in maintaining the balance of the activities of lymphocytes. Constant НHVI spreading is largely explained by transition of primary infection to potentially reactivating latent form, since latent virus is unavailable to immune recognition and medicines. The genome editing system CRISPR/Cas9 can recognize and modify not only active but also latent viruses. The promising pilot results with the use of this system offer the possibility of developing innovative technologies for НHV elimination and НHVI eradication.

摘要

本综述介绍了所有已知人类疱疹病毒(HHVs)在女性生殖道中的传播数据。据世界卫生组织统计,全球近5亿人患有由HHVs引起的生殖器感染。在女性上、下生殖道的各种炎症性疾病(阴道炎和宫颈炎)、宫外孕(输卵管)、不孕症(宫颈管、子宫内膜和卵巢)中均检测到HHVs。在体外受精(IVF)失败后的卵母细胞中首次发现了单纯疱疹病毒1型(HSV-1)。HHVs对从受孕到分娩的整个生殖过程产生负面影响。已证实,HSV、巨细胞病毒(CMV)和人类疱疹病毒6型(HHV-6)会显著增加自然流产、早产和死产的风险。宫内HHV感染是先天性畸形的主要原因。本文还综述了生殖器疱疹病毒感染(HHVI)中的体液免疫和细胞免疫数据。阴道内HSV-2感染会改变阴道黏膜的细胞组成,即与从血液中动员的细胞一起,驻留记忆T细胞(TRM)、自然杀伤细胞(NK细胞)和调节性T细胞(Treg)发挥保护作用,其功能在于维持淋巴细胞活动的平衡。HHVI的持续传播很大程度上是由于原发性感染转变为潜在的再激活潜伏形式,因为潜伏病毒无法被免疫识别和药物作用。基因组编辑系统CRISPR/Cas9不仅可以识别和修饰活跃病毒,还可以识别和修饰潜伏病毒。使用该系统取得的有前景的初步结果为开发消除HHV和根除HHVI的创新技术提供了可能性。

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