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经直肠感染的豚尾猕猴体内SIV(Mne)快速传播后的黏膜抗体表达

Mucosal antibody expression following rapid SIV(Mne) dissemination in intrarectally infected Macaca nemestrina.

作者信息

Kuller L, Thompson J, Watanabe R, Iskandriati D, Alpers C E, Morton W R, Agy M B

机构信息

Washington Regional Primate Research Center, University of Washington, Seattle 98195-7330, USA.

出版信息

AIDS Res Hum Retroviruses. 1998 Oct 10;14(15):1345-56. doi: 10.1089/aid.1998.14.1345.

Abstract

The early kinetics of antibody expression following transmucosal infection by SIV(Mne) were examined in several mucosal compartments in Macaca nemestrina. Five male-female pairs of macaques were inoculated intrarectally with SIV(Mne) E11S, a biological clone, and serially euthanized at 1, 2, 4, 8, and 12 weeks postinoculation. Plasma, tears, saliva, rectal secretions, and vaginal washes were collected serially and just prior to euthanasia. Both total and SIV-specific IgG and IgA levels were measured by immunoglobulin isotype-specific quantitative enzyme-linked immunosorbent assays (ELISAs), and were further examined by conventional and enhanced chemiluminescence (ECL) immunoblots. Virus coculture, polymerase chain reaction, and in situ hybridization assays revealed the systemic spread of virus as early as 1 week postinoculation in 8 of 10 animals. ECL immunoblots detected SIV-specific antibodies in mucosal samples collected 1 week postinoculation. The most dramatic increases in both total and SIV-specific IgA levels were detected in rectal secretion samples. In contrast, plasma and nonrectal mucosal samples from the same time points increased only slightly, suggesting that the most robust antibody response occurred at the portal of infection. Our results show that the SIV-infected macaque is an excellent model for studies designed to assess mucosal immune responses to primate lentivirus infections. Additional studies will assess the correlation between the antiviral protection afforded by candidate vaccines and mucosal antibody responses.

摘要

在豚尾猕猴的多个黏膜腔室中,研究了SIV(Mne)经黏膜感染后抗体表达的早期动力学。将五对雌雄猕猴经直肠接种生物克隆株SIV(Mne)E11S,并在接种后1、2、4、8和12周依次实施安乐死。在每次安乐死之前,连续采集血浆、眼泪、唾液、直肠分泌物和阴道灌洗液。通过免疫球蛋白同种型特异性定量酶联免疫吸附测定(ELISA)测量总IgG和IgA以及SIV特异性IgG和IgA水平,并通过传统和增强化学发光(ECL)免疫印迹进一步检测。病毒共培养、聚合酶链反应和原位杂交试验显示,在接种后1周,10只动物中有8只出现病毒的全身扩散。ECL免疫印迹在接种后1周采集的黏膜样本中检测到SIV特异性抗体。在直肠分泌物样本中检测到总IgA和SIV特异性IgA水平的最显著增加。相比之下,同一时间点的血浆和非直肠黏膜样本仅略有增加,这表明最强烈的抗体反应发生在感染门户。我们的结果表明,SIV感染的猕猴是用于评估对灵长类慢病毒感染的黏膜免疫反应的研究的优秀模型。更多研究将评估候选疫苗提供的抗病毒保护与黏膜抗体反应之间的相关性。

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