title: Visualization and quantification of simian immunodeficiency virus-infected cells using non-invasive molecular imaging.
abstract: In vivo imaging can provide real-time information and three-dimensional (3D) non-invasive images of deep tissues and organs, including the brain, whilst allowing longitudinal observation of the same animals, thus eliminating potential variation between subjects. Current in vivo imaging technologies, such as magnetic resonance imaging (MRI), positron emission tomography-computed tomography (PET-CT) and bioluminescence imaging (BLI), can be used to pinpoint the spatial location of target cells, which is urgently needed for revealing human immunodeficiency virus (HIV) dissemination in real-time and HIV-1 reservoirs during suppressive antiretroviral therapy (ART). To demonstrate that in vivo imaging can be used to visualize and quantify simian immunodeficiency virus (SIV)-transduced cells, we genetically engineered SIV to carry different imaging reporters. Based on the expression of the reporter genes, we could visualize and quantify the SIV-transduced cells via vesicular stomatitis virus glycoprotein pseudotyping in a mouse model using BLI, PET-CT or MRI. We also engineered a chimeric EcoSIV for in vivo infection study. Our results demonstrated that BLI is sensitive enough to detect as few as five single cells transduced with virus, whilst PET-CT can provide 3D images of the spatial location of as few as 10 000 SIV-infected cells. We also demonstrated that MRI can provide images with high spatial resolution in a 3D anatomical context to distinguish a small population of SIV-transduced cells. The in vivo imaging platform described here can potentially serve as a powerful tool to visualize lentiviral infection, including when and where viraemia rebounds, and how reservoirs are formed and maintained during latency or suppressive ART.
authors: Department of Radiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
authors: Jiasheng
authors: J
authors: Song
authors: Department of Radiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
authors: Zhengxin
authors: Z
authors: Cai
authors: Department of Radiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
authors: Alexander G
authors: AG
authors: White
authors: Department of Radiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
authors: Tao
authors: T
authors: Jin
authors: Department of Radiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
authors: Xiaolei
authors: X
authors: Wang
authors: Department of Oncology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
authors: Deepak
authors: D
authors: Kadayakkara
authors: Department of Radiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
authors: Carolyn J
authors: CJ
authors: Anderson
authors: Division of Infectious Diseases, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
authors: Zandrea
authors: Z
authors: Ambrose
authors: Department of Radiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
authors: Won-Bin
authors: WB
authors: Young
mesh_terms: D000818:Animals; D017930:Genes, Reporter; D021621:Imaging, Three-Dimensional; D008163:Luminescent Measurements / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008819:Mice, Nude; D057054:Molecular Imaging / Q000379:methods*; D049268:Positron-Emission Tomography / Q000379:methods; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000254:growth & development*; D014161:Transduction, Genetic; D018116:Vesiculovirus / Q000235:genetics