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整合素 αβ 在 HIV 发病机制和治疗中的作用。

The Role of Integrin αβ in HIV Pathogenesis and Treatment.

机构信息

Laboratory of Immunoregulation, National Institutes of Allergy & Infectious Diseases, National Institutes of Health, 10 Center Drive Rm 6A08, Bethesda, MD, 20814, USA.

Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, 68198, USA.

出版信息

Curr HIV/AIDS Rep. 2018 Apr;15(2):127-135. doi: 10.1007/s11904-018-0382-3.

Abstract

PURPOSE OF REVIEW

Acute HIV infection is characterized by high-level viral replication throughout the body's lymphoid system, particularly in gut-associated lymphoid tissues resulting in damage to structural components of gut tissue. This damage is irreversible and believed to contribute to the development of immune deficiencies. Antiretroviral therapy (ART) does not restore gut structure and function. Studies in macaques point to an alternative treatment strategy that may ameliorate gut damage. Integrin αβ mediates the homing of lymphocytes to gut tissues. Vedolizumab, a monoclonal antibody (mAb) antagonist of αβ, has demonstrated efficacy and has been approved for the treatment of inflammatory bowel disease in humans. Here, we describe our current knowledge, and the gaps in our understanding, of the role of αβ in HIV pathogenesis and treatment.

RECENT FINDINGS

When administered to macaques prior to infection, a nonhuman primate analogue of vedolizumab prevents transmission of SIV. In combination with ART, this mAb facilitates durable virologic control following treatment interruption. Targeting αβ represents a novel therapeutic approach to prevent and treat HIV infection.

摘要

目的综述

急性 HIV 感染的特征是全身淋巴系统中的病毒复制水平高,特别是在肠道相关淋巴组织中,导致肠道组织的结构成分受损。这种损伤是不可逆转的,据信会导致免疫缺陷的发展。抗逆转录病毒疗法(ART)不能恢复肠道结构和功能。在猕猴中的研究指出了一种可能改善肠道损伤的替代治疗策略。整合素 αβ 介导淋巴细胞归巢到肠道组织。Vedolizumab 是一种 αβ 的单克隆抗体(mAb)拮抗剂,已被证明在人类治疗炎症性肠病方面有效,并已获得批准。在这里,我们描述了我们目前对 αβ 在 HIV 发病机制和治疗中的作用的了解,以及我们理解中的空白。

最新发现

在感染前给予猕猴时,vedolizumab 的非人类灵长类动物类似物可预防 SIV 的传播。与 ART 联合使用时,这种 mAb 可在治疗中断后实现持久的病毒学控制。靶向 αβ 代表了一种预防和治疗 HIV 感染的新型治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb7c/5882766/18b6c24cab1b/11904_2018_382_Fig1_HTML.jpg

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