Whole-body immunoPET reveals active SIV dynamics in viremic and antiretroviral therapy-treated macaques

全身免疫 PET 揭示病毒血症和抗逆转录病毒疗法治疗的恒河猴中活跃的 SIV 动态

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作者:Philip J Santangelo, Kenneth A Rogers, Chiara Zurla, Emmeline L Blanchard, Sanjeev Gumber, Karen Strait, Fawn Connor-Stroud, David M Schuster, Praveen K Amancha, Jung Joo Hong, Siddappa N Byrareddy, James A Hoxie, Brani Vidakovic, Aftab A Ansari, Eric Hunter, Francois Villinger

Abstract

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.

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