Whole-body immunoPET reveals active SIV dynamics in viremic and antiretroviral therapy-treated macaques.
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.
Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia, USA.
Philip J
PJ
Santangelo
Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA.
Kenneth A
KA
Rogers
Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia, USA.
Chiara
C
Zurla
Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia, USA.
Emmeline L
EL
Blanchard
1] Division of Pathology, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA. [2] Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.
Sanjeev
S
Gumber
Division of Veterinary Medicine, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA.
Karen
K
Strait
Division of Veterinary Medicine, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA.
Fawn
F
Connor-Stroud
Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, Georgia, USA.
David M
DM
Schuster
Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA.
Praveen K
PK
Amancha
Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA.
Jung Joo
JJ
Hong
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.
Siddappa N
SN
Byrareddy
Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
James A
JA
Hoxie
Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia, USA.
Brani
B
Vidakovic
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.
Aftab A
AA
Ansari
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.
Eric
E
Hunter
1] Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA. [2] Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.
Francois
F
Villinger
D000225:Adenine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000818:Animals; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D003301:Copper Radioisotopes; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000068679:Emtricitabine; D007150:Immunohistochemistry; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D009287:Naphthyridines / Q000627:therapeutic use; D063065:Organophosphonates / Q000627:therapeutic use; D049268:Positron-Emission Tomography / Q000379:methods*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D015302:Simian Immunodeficiency Virus; D000068698:Tenofovir; D014759:Viral Envelope Proteins / Q000378:metabolism; D014766:Viremia; D014779:Virus Replication; D051598:Whole Body Imaging / Q000379:methods*
D044966:Anti-Retroviral Agents; D003301:Copper Radioisotopes; C488294:L870812; D008562:Membrane Glycoproteins; D009287:Naphthyridines; D063065:Organophosphonates; D014759:Viral Envelope Proteins; C069623:gp120 protein, Simian immunodeficiency virus; D003841:Deoxycytidine; D000068698:Tenofovir; D000068679:Emtricitabine; D000225:Adenine