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慢性诺如病毒感染期间的宿主内病毒进化。

Intrahost viral evolution during chronic sapovirus infections.

机构信息

Institute of Virology, Leipzig University, Leipzig, Germany Johannisallee 30, 04103, Leipzig, Germany.

Institute of Virology, Leipzig University, Leipzig, Germany Johannisallee 30, 04103, Leipzig, Germany.

出版信息

J Clin Virol. 2019 Apr;113:1-7. doi: 10.1016/j.jcv.2019.02.001. Epub 2019 Feb 7.

Abstract

BACKGROUND

Sapovirus is a common cause of self-limiting diarrhea. In immunocompromised individuals chronic infections occur, but are incompletely investigated.

OBJECTIVES

To investigate viral evolution in immunocompromised hosts during chronic sapovirus infection.

STUDY DESIGN

From January 2010 to September 2018 stool samples of 5333 in-patients were analyzed for the presence of sapovirus RNA by real-time RT-PCR. In follow-up samples of chronic diarrhea cases nucleic acid sequencing of sapovirus genomes was performed. Amino acid mutations were identified by alignments and compared to data from GenBank. Sapovirus genotypes were assessed by phylogenetic analysis of viral capsid gene (VP1).

RESULTS

Sapovirus RNA was present in 146 stool samples of 95 patients (1.8%), most frequently in young children and infants. In patients older than 14 years, sapoviruses were exclusively detected in immunocompromised patients. Chronic diarrhea occurred in almost one third of the sapovirus positive immunocompromised individuals (n = 5) and was established by different sapovirus genotypes (GI.2, GII.1, GII.3). The maximum observed duration of sapovirus shedding was 119 days. Accumulation of amino acid mutations during chronic infection was most often detected within VP1 P2 protruding subdomain. Reduction of immunosuppression was associated with decrease of viral load and clearance of sapovirus in stool.

CONCLUSIONS

Clinicians should consider immunocompromised individuals at risk to develop chronic diarrhea due to persistence of SaV infection. The identified VP1 mutations contribute to an understanding of sapovirus-host interactions. For further conclusions regarding virus immune escape and altered viral fitness structural data on sapovirus capsid and virus/receptor complex are necessary.

摘要

背景

诺如病毒是导致自限性腹泻的常见原因。在免疫功能低下的个体中会发生慢性感染,但研究并不完全。

目的

研究免疫功能低下宿主慢性诺如病毒感染过程中的病毒进化。

研究设计

从 2010 年 1 月至 2018 年 9 月,通过实时 RT-PCR 分析了 5333 例住院患者的粪便样本中是否存在诺如病毒 RNA。对慢性腹泻病例的随访样本进行了诺如病毒基因组的核酸测序。通过比对和与 GenBank 数据比较来鉴定氨基酸突变。通过病毒衣壳基因(VP1)的系统发育分析评估诺如病毒基因型。

结果

在 95 例患者的 146 份粪便样本中(1.8%)检测到诺如病毒 RNA,最常见于幼儿和婴儿。在 14 岁以上的患者中,诺如病毒仅在免疫功能低下的患者中检出。几乎三分之一的诺如病毒阳性免疫功能低下个体(n=5)出现慢性腹泻,并通过不同的诺如病毒基因型(GI.2、GII.1、GII.3)确立。观察到的诺如病毒脱落最长持续时间为 119 天。在慢性感染过程中,VP1 P2 突出亚域内氨基酸突变的积累最为常见。减少免疫抑制与降低粪便中的病毒载量和清除诺如病毒有关。

结论

临床医生应考虑免疫功能低下的个体有发生持续诺如病毒感染导致慢性腹泻的风险。鉴定的 VP1 突变有助于了解诺如病毒-宿主相互作用。为了进一步了解病毒免疫逃逸和改变的病毒适应性,需要有关诺如病毒衣壳和病毒/受体复合物的结构数据。

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