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减毒致病性突变体在生殖道中的传染性。

Infectivity of a pathogenicity-attenuated mutant in the genital tract.

作者信息

Li Caiting, Liu Zhaoyang, Hua Yaoqin, Ma Chunguang, Zhong Guangming

机构信息

Department of Dermatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.

Department of Microbiology, Immunology, and Molecular Genetics, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.

出版信息

Infect Immun. 2025 Jun 10;93(6):e0058824. doi: 10.1128/iai.00588-24. Epub 2025 May 23.

Abstract

A mutant designated as intrOv was evaluated as an acellular ral vaccine ector because it can induce protection in the genital tract following oral inoculation but does not elicit genital pathology following intravaginal infection. However, the mechanism of intrOv's attenuation is unclear. Here, we report that few live organisms were recovered from vaginal swabs during the early stage of intrOv intravaginal infection in mice. At a low inoculating dose, an isogenic wild-type control strain established a productive infection, while intrOv failed to do so. Although a higher inoculating dose allowed intrOv and its control to productively infect mice, fewer live intrOv than the control organisms were recovered from the lower genital tract tissues on day 3 post-infection. By day 7, animals infected with intrOv or the control shed similar numbers of live organisms, suggesting that intrOv's deficiency on day 3 was transient. Consistently, intrOv reduced invasion of epithelial cells but maintained as robust intracellular replication as its control. Our results correlate intrOv's delay in infecting the lower genital tissues and reduction in invading epithelial cells with its attenuation in genital pathogenicity, laying the foundation for further revealing the mechanisms of intrOv's attenuation in pathogenicity during genital tract infection.

摘要

一种名为intrOv的突变体被评估为一种无细胞狂犬病疫苗载体,因为它在口服接种后能在生殖道诱导产生保护作用,但在阴道内感染后不会引发生殖道病变。然而,intrOv减毒的机制尚不清楚。在此,我们报告在小鼠阴道内感染intrOv的早期阶段,从阴道拭子中回收的活生物体很少。在低接种剂量下,同基因野生型对照菌株能建立有效的感染,而intrOv则不能。尽管较高的接种剂量能使intrOv及其对照有效地感染小鼠,但在感染后第3天,从下生殖道组织中回收的活intrOv比对照生物体少。到第7天,感染intrOv或对照的动物排出的活生物体数量相似,这表明intrOv在第3天的缺陷是短暂的。一致地,intrOv减少了对上皮细胞的侵袭,但保持了与对照一样强大的细胞内复制能力。我们的结果将intrOv在下生殖道组织感染中的延迟以及对上皮细胞侵袭的减少与其在生殖道致病性的减弱相关联,为进一步揭示intrOv在生殖道感染期间致病性减弱的机制奠定了基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d310/12150688/245874fd467c/iai.00588-24.f001.jpg

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