Santangelo Philip J, Rogers Kenneth A, Zurla Chiara, Blanchard Emmeline L, Gumber Sanjeev, Strait Karen, Connor-Stroud Fawn, Schuster David M, Amancha Praveen K, Hong Jung Joo, Byrareddy Siddappa N, Hoxie James A, Vidakovic Brani, Ansari Aftab A, Hunter Eric, Villinger Francois
Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia, USA.
Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA.
Nat Methods. 2015 May;12(5):427-32. doi: 10.1038/nmeth.3320. Epub 2015 Mar 9.
The detection of viral dynamics and localization in the context of controlled HIV infection remains a challenge and is limited to blood and biopsies. We developed a method to capture total-body simian immunodeficiency virus (SIV) replication using immunoPET (antibody-targeted positron emission tomography). The administration of a poly(ethylene glycol)-modified, (64)Cu-labeled SIV Gp120-specific antibody led to readily detectable signals in the gastrointestinal and respiratory tract, lymphoid tissues and reproductive organs of viremic monkeys. Viral signals were reduced in aviremic antiretroviral-treated monkeys but detectable in colon, select lymph nodes, small bowel, nasal turbinates, the genital tract and lung. In elite controllers, virus was detected primarily in foci in the small bowel, select lymphoid areas and the male reproductive tract, as confirmed by quantitative reverse-transcription PCR (qRT-PCR) and immunohistochemistry. This real-time, in vivo viral imaging method has broad applications to the study of immunodeficiency virus pathogenesis, drug and vaccine development, and the potential for clinical translation.
在可控的HIV感染情况下检测病毒动态和定位仍然是一项挑战,并且仅限于血液和活检。我们开发了一种使用免疫PET(抗体靶向正电子发射断层扫描)来捕获全身猴免疫缺陷病毒(SIV)复制的方法。给予聚乙二醇修饰的、(64)Cu标记的SIV Gp120特异性抗体后,在病毒血症猴子的胃肠道、呼吸道、淋巴组织和生殖器官中产生了易于检测到的信号。在接受抗逆转录病毒治疗的无病毒血症猴子中,病毒信号减少,但在结肠、选定的淋巴结、小肠、鼻甲、生殖道和肺部仍可检测到。在精英控制者中,通过定量逆转录PCR(qRT-PCR)和免疫组织化学证实,病毒主要在小肠的病灶、选定的淋巴区域和男性生殖道中被检测到。这种实时体内病毒成像方法在免疫缺陷病毒发病机制研究、药物和疫苗开发以及临床转化潜力方面具有广泛应用。