Zoey K Wallis, Yingshan Wei, Lily M Ceraso, Cecily C Midkiff, Addison Q Amadeck, Yiwei Wang, Andrew D Miller, Robert V Blair, Kenneth C Williams
{"title":"新的神经周围通路和猴免疫缺陷病毒感染的巨噬细胞运输出中枢神经系统的动力学。","authors":"Zoey K Wallis, Yingshan Wei, Lily M Ceraso, Cecily C Midkiff, Addison Q Amadeck, Yiwei Wang, Andrew D Miller, Robert V Blair, Kenneth C Williams","doi":"10.1016/j.ajpath.2025.07.014","DOIUrl":null,"url":null,"abstract":"<p><p>A challenge to eradicate HIV is the central nervous system (CNS) reservoir and unknown mechanisms-pathways by which infected macrophages can exit. We used intracisternal injection of superparamagnetic iron oxide nanoparticles (SPIONs), some of which had different internal immune fluorescence to define perineural pathways of SPION<sup>+</sup> macrophage traffic in SIV-infected animals with AIDS, on antiretroviral therapy (ART) and with ART interruption. SPION<sup>+</sup> macrophages are identified in central (spinal cord and cranial nerves) and peripheral (dorsal root ganglia) sites. In noninfected animals, SPION<sup>+</sup> macrophages traffic out normally. With SIV infection, SPION<sup>+</sup> macrophages accumulate in the CNS, and there are decreased numbers that traffic out. SIV<sup>-</sup> RNA and gp41 SPION<sup>+</sup> macrophages are found in cranial nerves and dorsal root ganglion that are significantly reduced, but not eliminated, with ART. Using SPIONs with two different internal fluorescences, injected early and late after SIV infection, we find AIDS animals have greater numbers of early injected SPION<sup>+</sup> macrophages within cranial nerves, consistent with reduced traffic late. With ART, there are greater numbers of late and dual (early and late) labeled SPION<sup>+</sup> macrophages in the periphery, that return to levels found in AIDS animals following ART interruption. These findings reveal a novel pathway by which CNS macrophages can redistribute virus from the CNS to the periphery that persists despite ART.</p>","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":" ","pages":""},"PeriodicalIF":3.6000,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Novel Perineural Pathways and the Dynamics of SIV-Infected Macrophage Trafficking Out of the Central Nervous System.\",\"authors\":\"Zoey K Wallis, Yingshan Wei, Lily M Ceraso, Cecily C Midkiff, Addison Q Amadeck, Yiwei Wang, Andrew D Miller, Robert V Blair, Kenneth C Williams\",\"doi\":\"10.1016/j.ajpath.2025.07.014\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>A challenge to eradicate HIV is the central nervous system (CNS) reservoir and unknown mechanisms-pathways by which infected macrophages can exit. We used intracisternal injection of superparamagnetic iron oxide nanoparticles (SPIONs), some of which had different internal immune fluorescence to define perineural pathways of SPION<sup>+</sup> macrophage traffic in SIV-infected animals with AIDS, on antiretroviral therapy (ART) and with ART interruption. SPION<sup>+</sup> macrophages are identified in central (spinal cord and cranial nerves) and peripheral (dorsal root ganglia) sites. In noninfected animals, SPION<sup>+</sup> macrophages traffic out normally. With SIV infection, SPION<sup>+</sup> macrophages accumulate in the CNS, and there are decreased numbers that traffic out. SIV<sup>-</sup> RNA and gp41 SPION<sup>+</sup> macrophages are found in cranial nerves and dorsal root ganglion that are significantly reduced, but not eliminated, with ART. Using SPIONs with two different internal fluorescences, injected early and late after SIV infection, we find AIDS animals have greater numbers of early injected SPION<sup>+</sup> macrophages within cranial nerves, consistent with reduced traffic late. With ART, there are greater numbers of late and dual (early and late) labeled SPION<sup>+</sup> macrophages in the periphery, that return to levels found in AIDS animals following ART interruption. These findings reveal a novel pathway by which CNS macrophages can redistribute virus from the CNS to the periphery that persists despite ART.</p>\",\"PeriodicalId\":7623,\"journal\":{\"name\":\"American Journal of Pathology\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.6000,\"publicationDate\":\"2025-09-02\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"American Journal of Pathology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.ajpath.2025.07.014\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PATHOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"American Journal of Pathology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.ajpath.2025.07.014","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PATHOLOGY","Score":null,"Total":0}
Novel Perineural Pathways and the Dynamics of SIV-Infected Macrophage Trafficking Out of the Central Nervous System.
A challenge to eradicate HIV is the central nervous system (CNS) reservoir and unknown mechanisms-pathways by which infected macrophages can exit. We used intracisternal injection of superparamagnetic iron oxide nanoparticles (SPIONs), some of which had different internal immune fluorescence to define perineural pathways of SPION+ macrophage traffic in SIV-infected animals with AIDS, on antiretroviral therapy (ART) and with ART interruption. SPION+ macrophages are identified in central (spinal cord and cranial nerves) and peripheral (dorsal root ganglia) sites. In noninfected animals, SPION+ macrophages traffic out normally. With SIV infection, SPION+ macrophages accumulate in the CNS, and there are decreased numbers that traffic out. SIV- RNA and gp41 SPION+ macrophages are found in cranial nerves and dorsal root ganglion that are significantly reduced, but not eliminated, with ART. Using SPIONs with two different internal fluorescences, injected early and late after SIV infection, we find AIDS animals have greater numbers of early injected SPION+ macrophages within cranial nerves, consistent with reduced traffic late. With ART, there are greater numbers of late and dual (early and late) labeled SPION+ macrophages in the periphery, that return to levels found in AIDS animals following ART interruption. These findings reveal a novel pathway by which CNS macrophages can redistribute virus from the CNS to the periphery that persists despite ART.
期刊介绍:
The American Journal of Pathology, official journal of the American Society for Investigative Pathology, published by Elsevier, Inc., seeks high-quality original research reports, reviews, and commentaries related to the molecular and cellular basis of disease. The editors will consider basic, translational, and clinical investigations that directly address mechanisms of pathogenesis or provide a foundation for future mechanistic inquiries. Examples of such foundational investigations include data mining, identification of biomarkers, molecular pathology, and discovery research. Foundational studies that incorporate deep learning and artificial intelligence are also welcome. High priority is given to studies of human disease and relevant experimental models using molecular, cellular, and organismal approaches.