HIV感染者大脑基因组学研究的最新进展和未来之路。

IF 3.7 2区 医学 Q2 INFECTIOUS DISEASES
Current HIV/AIDS Reports Pub Date : 2023-12-01 Epub Date: 2023-11-10 DOI:10.1007/s11904-023-00675-9
Amara Plaza-Jennings, Schahram Akbarian
{"title":"HIV感染者大脑基因组学研究的最新进展和未来之路。","authors":"Amara Plaza-Jennings, Schahram Akbarian","doi":"10.1007/s11904-023-00675-9","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose of review: </strong>The adult human brain harbors billions of microglia and other myeloid and lymphoid cells highly susceptible to HIV infection and retroviral insertion into the nuclear DNA. HIV infection of the brain is important because the brain is a potentially large reservoir site that may be a barrier to HIV cure strategies and because infection can lead to the development of HIV-associated neurocognitive disorder. To better understand both the central nervous system (CNS) reservoir and how it can cause neurologic dysfunction, novel genomic, epigenomic, transcriptomic, and proteomic approaches need to be employed. Several characteristics of the reservoir are important to learn, including where the virus integrates, whether integrated proviruses are intact or defective, whether integrated proviruses can be reactivated from a latent state to seed ongoing infection, and how this all impacts brain function.</p><p><strong>Recent findings: </strong>Here, we discuss similarities and differences of viral integration sites between brain and blood and discuss evidence for and against the hypothesis that in the absence of susceptible T-lymphocytes in the periphery, the virus housing in the infected brain is not able to sustain a systemic infection. Moreover, microglia from HIV + brains across a wide range of disease severity appear to share one type of common alteration, which is defined by downregulated expression, and repressive chromosomal compartmentalization, for microglial genes regulating synaptic connectivity. Therefore, viral infection of the brain, including in immunocompetent cases with near-normal levels of CD4 blood lymphocytes, could be associated with an early disruption in microglia-dependent neuronal support functions, contributing to cognitive and neurological deficits in people living with HIV.</p>","PeriodicalId":10930,"journal":{"name":"Current HIV/AIDS Reports","volume":" ","pages":"357-367"},"PeriodicalIF":3.7000,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10719125/pdf/","citationCount":"0","resultStr":"{\"title\":\"Genomic Exploration of the Brain in People Infected with HIV-Recent Progress and the Road Ahead.\",\"authors\":\"Amara Plaza-Jennings, Schahram Akbarian\",\"doi\":\"10.1007/s11904-023-00675-9\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose of review: </strong>The adult human brain harbors billions of microglia and other myeloid and lymphoid cells highly susceptible to HIV infection and retroviral insertion into the nuclear DNA. HIV infection of the brain is important because the brain is a potentially large reservoir site that may be a barrier to HIV cure strategies and because infection can lead to the development of HIV-associated neurocognitive disorder. To better understand both the central nervous system (CNS) reservoir and how it can cause neurologic dysfunction, novel genomic, epigenomic, transcriptomic, and proteomic approaches need to be employed. Several characteristics of the reservoir are important to learn, including where the virus integrates, whether integrated proviruses are intact or defective, whether integrated proviruses can be reactivated from a latent state to seed ongoing infection, and how this all impacts brain function.</p><p><strong>Recent findings: </strong>Here, we discuss similarities and differences of viral integration sites between brain and blood and discuss evidence for and against the hypothesis that in the absence of susceptible T-lymphocytes in the periphery, the virus housing in the infected brain is not able to sustain a systemic infection. Moreover, microglia from HIV + brains across a wide range of disease severity appear to share one type of common alteration, which is defined by downregulated expression, and repressive chromosomal compartmentalization, for microglial genes regulating synaptic connectivity. Therefore, viral infection of the brain, including in immunocompetent cases with near-normal levels of CD4 blood lymphocytes, could be associated with an early disruption in microglia-dependent neuronal support functions, contributing to cognitive and neurological deficits in people living with HIV.</p>\",\"PeriodicalId\":10930,\"journal\":{\"name\":\"Current HIV/AIDS Reports\",\"volume\":\" \",\"pages\":\"357-367\"},\"PeriodicalIF\":3.7000,\"publicationDate\":\"2023-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10719125/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Current HIV/AIDS Reports\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s11904-023-00675-9\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2023/11/10 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"INFECTIOUS DISEASES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current HIV/AIDS Reports","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s11904-023-00675-9","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/11/10 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"INFECTIOUS DISEASES","Score":null,"Total":0}
引用次数: 0

摘要

综述目的:成年人脑中含有数十亿小胶质细胞和其他骨髓和淋巴细胞,这些细胞对HIV感染和逆转录病毒插入细胞核DNA高度敏感。大脑中的HIV感染很重要,因为大脑是一个潜在的大储存部位,可能是HIV治疗策略的障碍,而且感染会导致HIV相关神经认知障碍的发展。为了更好地了解中枢神经系统(CNS)库及其如何导致神经功能障碍,需要采用新的基因组、表观基因组、转录组和蛋白质组学方法。宿主的几个特征很重要,包括病毒在哪里整合,整合的前病毒是完整的还是有缺陷的,整合的原病毒是否可以从潜伏状态重新激活以引发持续的感染,以及这一切如何影响大脑功能。最近的发现:在这里,我们讨论了大脑和血液之间病毒整合位点的异同,并讨论了支持和反对以下假设的证据:在外周缺乏易感T淋巴细胞的情况下,感染大脑中的病毒外壳无法维持系统性感染。此外,来自HIV的小胶质细胞 + 不同疾病严重程度的大脑似乎都有一种常见的改变,即调节突触连接的小胶质细胞基因表达下调和染色体区室化抑制。因此,大脑的病毒感染,包括CD4血淋巴细胞水平接近正常的免疫活性病例,可能与小胶质细胞依赖性神经元支持功能的早期破坏有关,导致HIV感染者的认知和神经功能缺陷。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Genomic Exploration of the Brain in People Infected with HIV-Recent Progress and the Road Ahead.

Genomic Exploration of the Brain in People Infected with HIV-Recent Progress and the Road Ahead.

Purpose of review: The adult human brain harbors billions of microglia and other myeloid and lymphoid cells highly susceptible to HIV infection and retroviral insertion into the nuclear DNA. HIV infection of the brain is important because the brain is a potentially large reservoir site that may be a barrier to HIV cure strategies and because infection can lead to the development of HIV-associated neurocognitive disorder. To better understand both the central nervous system (CNS) reservoir and how it can cause neurologic dysfunction, novel genomic, epigenomic, transcriptomic, and proteomic approaches need to be employed. Several characteristics of the reservoir are important to learn, including where the virus integrates, whether integrated proviruses are intact or defective, whether integrated proviruses can be reactivated from a latent state to seed ongoing infection, and how this all impacts brain function.

Recent findings: Here, we discuss similarities and differences of viral integration sites between brain and blood and discuss evidence for and against the hypothesis that in the absence of susceptible T-lymphocytes in the periphery, the virus housing in the infected brain is not able to sustain a systemic infection. Moreover, microglia from HIV + brains across a wide range of disease severity appear to share one type of common alteration, which is defined by downregulated expression, and repressive chromosomal compartmentalization, for microglial genes regulating synaptic connectivity. Therefore, viral infection of the brain, including in immunocompetent cases with near-normal levels of CD4 blood lymphocytes, could be associated with an early disruption in microglia-dependent neuronal support functions, contributing to cognitive and neurological deficits in people living with HIV.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Current HIV/AIDS Reports
Current HIV/AIDS Reports INFECTIOUS DISEASES-
CiteScore
8.10
自引率
2.20%
发文量
45
期刊介绍: This journal intends to provide clear, insightful, balanced contributions by international experts that review the most important, recently published clinical findings related to the diagnosis, treatment, management, and prevention of HIV/AIDS. We accomplish this aim by appointing international authorities to serve as Section Editors in key subject areas, such as antiretroviral therapies, behavioral aspects of management, and metabolic complications and comorbidity. Section Editors, in turn, select topics for which leading experts contribute comprehensive review articles that emphasize new developments and recently published papers of major importance, highlighted by annotated reference lists. An international Editorial Board reviews the annual table of contents, suggests articles of special interest to their country/region, and ensures that topics are current and include emerging research. Commentaries from well-known figures in the field are also provided.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信