Rachel M Podgorski, Jake A Robinson, Mandy D Smith, Suvadip Mallick, Huaqing Zhao, Ronald S Veazey, Dennis L Kolson, Katharine J Bar, Tricia H Burdo
{"title":"在恒河猴中，传播/创始人SHIV.D在大脑中复制，引起神经病变，并在联合抗逆转录病毒治疗中持续存在。","authors":"Rachel M Podgorski, Jake A Robinson, Mandy D Smith, Suvadip Mallick, Huaqing Zhao, Ronald S Veazey, Dennis L Kolson, Katharine J Bar, Tricia H Burdo","doi":"10.1186/s12977-023-00628-5","DOIUrl":null,"url":null,"abstract":"<p><p>A biologically relevant non-human primate (NHP) model of HIV persistence in the central nervous system (CNS) is necessary. Most current NHP/SIV models of HIV infection fail to recapitulate viral persistence in the CNS without encephalitis or fail to employ viruses that authentically represent the ongoing HIV-1 pandemic. Here, we demonstrate viral replication in the brain and neuropathogenesis after combination antiretroviral therapy (ART) in rhesus macaques (RMs) using novel macrophage-tropic transmitted/founder (TF) simian-human immunodeficiency virus SHIV.D.191,859 (SHIV.D). Quantitative immunohistochemistry (IHC) and DNA/RNAscope in situ hybridization (ISH) were performed on three brain regions from six SHIV.D-infected RMs; two necropsied while viremic, two during analytical treatment interruptions, and two on suppressive ART. We demonstrated myeloid-mediated neuroinflammation, viral replication, and proviral DNA in the brain in all animals. These results demonstrate that TF SHIV.D models native HIV-1 CNS replication, pathogenesis, and persistence on ART in rhesus macaques.</p>","PeriodicalId":21123,"journal":{"name":"Retrovirology","volume":null,"pages":null},"PeriodicalIF":2.7000,"publicationDate":"2023-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10413509/pdf/","citationCount":"0","resultStr":"{\"title\":\"Transmitted/founder SHIV.D replicates in the brain, causes neuropathogenesis, and persists on combination antiretroviral therapy in rhesus macaques.\",\"authors\":\"Rachel M Podgorski, Jake A Robinson, Mandy D Smith, Suvadip Mallick, Huaqing Zhao, Ronald S Veazey, Dennis L Kolson, Katharine J Bar, Tricia H Burdo\",\"doi\":\"10.1186/s12977-023-00628-5\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>A biologically relevant non-human primate (NHP) model of HIV persistence in the central nervous system (CNS) is necessary. Most current NHP/SIV models of HIV infection fail to recapitulate viral persistence in the CNS without encephalitis or fail to employ viruses that authentically represent the ongoing HIV-1 pandemic. Here, we demonstrate viral replication in the brain and neuropathogenesis after combination antiretroviral therapy (ART) in rhesus macaques (RMs) using novel macrophage-tropic transmitted/founder (TF) simian-human immunodeficiency virus SHIV.D.191,859 (SHIV.D). Quantitative immunohistochemistry (IHC) and DNA/RNAscope in situ hybridization (ISH) were performed on three brain regions from six SHIV.D-infected RMs; two necropsied while viremic, two during analytical treatment interruptions, and two on suppressive ART. We demonstrated myeloid-mediated neuroinflammation, viral replication, and proviral DNA in the brain in all animals. These results demonstrate that TF SHIV.D models native HIV-1 CNS replication, pathogenesis, and persistence on ART in rhesus macaques.</p>\",\"PeriodicalId\":21123,\"journal\":{\"name\":\"Retrovirology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.7000,\"publicationDate\":\"2023-08-10\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10413509/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Retrovirology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s12977-023-00628-5\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"VIROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Retrovirology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12977-023-00628-5","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"VIROLOGY","Score":null,"Total":0}
Transmitted/founder SHIV.D replicates in the brain, causes neuropathogenesis, and persists on combination antiretroviral therapy in rhesus macaques.
A biologically relevant non-human primate (NHP) model of HIV persistence in the central nervous system (CNS) is necessary. Most current NHP/SIV models of HIV infection fail to recapitulate viral persistence in the CNS without encephalitis or fail to employ viruses that authentically represent the ongoing HIV-1 pandemic. Here, we demonstrate viral replication in the brain and neuropathogenesis after combination antiretroviral therapy (ART) in rhesus macaques (RMs) using novel macrophage-tropic transmitted/founder (TF) simian-human immunodeficiency virus SHIV.D.191,859 (SHIV.D). Quantitative immunohistochemistry (IHC) and DNA/RNAscope in situ hybridization (ISH) were performed on three brain regions from six SHIV.D-infected RMs; two necropsied while viremic, two during analytical treatment interruptions, and two on suppressive ART. We demonstrated myeloid-mediated neuroinflammation, viral replication, and proviral DNA in the brain in all animals. These results demonstrate that TF SHIV.D models native HIV-1 CNS replication, pathogenesis, and persistence on ART in rhesus macaques.
期刊介绍：
Retrovirology is an open access, online journal that publishes stringently peer-reviewed, high-impact articles on host-pathogen interactions, fundamental mechanisms of replication, immune defenses, animal models, and clinical science relating to retroviruses. Retroviruses are pleiotropically found in animals. Well-described examples include avian, murine and primate retroviruses.
Two human retroviruses are especially important pathogens. These are the human immunodeficiency virus, HIV, and the human T-cell leukemia virus, HTLV. HIV causes AIDS while HTLV-1 is the etiological agent for adult T-cell leukemia and HTLV-1-associated myelopathy/tropical spastic paraparesis. Retrovirology aims to cover comprehensively all aspects of human and animal retrovirus research.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
