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PET/CT targeted tissue sampling reveals virus specific dIgA can alter the distribution and localization of HIV after rectal exposure
- Source :
- PLoS Pathogens, Vol 17, Iss 6, p e1009632 (2021), PLoS Pathogens
- Publication Year :
- 2021
- Publisher :
- Public Library of Science (PLoS), 2021.
-
Abstract
- Human immunodeficiency virus (HIV) vaccines have not been successful in clinical trials. Dimeric IgA (dIgA) in the form of secretory IgA is the most abundant antibody class in mucosal tissues, making dIgA a prime candidate for potential HIV vaccines. We coupled Positron Emission Tomography (PET) imaging and fluorescent microscopy of 64Cu-labeled, photoactivatable-GFP HIV (PA-GFP-BaL) and fluorescently labeled dIgA to determine how dIgA antibodies influence virus interaction with mucosal barriers and viral penetration in colorectal tissue. Our results show that HIV virions rapidly disseminate throughout the colon two hours after exposure. The presence of dIgA resulted in an increase in virions and penetration depth in the transverse colon. Moreover, virions were found in the mesenteric lymph nodes two hours after viral exposure, and the presence of dIgA led to an increase in virions in mesenteric lymph nodes. Taken together, these technologies enable in vivo and in situ visualization of antibody-virus interactions and detailed investigations of early events in HIV infection.<br />Author summary Vaccines provide protection in humans by eliciting the production of antibodies when exposed to a specific pathogen. Currently, an effective human immunodeficiency virus (HIV) vaccine does not exist. Since the beginning of the HIV epidemic, approximately 38 million people have died, creating the need to develop an HIV vaccine. The most common antibody in the organs that are exposed to HIV is dimeric IgA (dIgA). Here, we used multiple imaging techniques to determine how HIV travels throughout the colon once introduced into the body and how dIgA influences HIV movement in the rectum. We found that dIgA increased the amount of HIV found in the colon, the distance it travelled, and the depth into tissues that HIV penetrated. dIgA also increased the amount of HIV in the mesenteric lymph nodes two hours after viral exposure. Our study shows these imaging technologies can be used to examine interactions between viruses and antibodies in early HIV infection in the natural context of the anatomy and physiology of the rhesus macaque model.
- Subjects :
- RNA viruses
Physiology
viruses
Human immunodeficiency virus (HIV)
HIV Infections
HIV Antibodies
Pathology and Laboratory Medicine
medicine.disease_cause
Biochemistry
Virions
Diagnostic Radiology
0302 clinical medicine
Immunodeficiency Viruses
Immune Physiology
Positron Emission Tomography Computed Tomography
Medicine and Health Sciences
Fluorescence microscope
Mesenteric lymph nodes
Biology (General)
Tomography
0303 health sciences
Immune System Proteins
biology
Radiology and Imaging
Immune complex
medicine.anatomical_structure
Medical Microbiology
Viral Pathogens
Viruses
Anatomy
Pathogens
Antibody
Research Article
Colon
Imaging Techniques
QH301-705.5
Immunology
Rectum
Neuroimaging
Viral Structure
Research and Analysis Methods
Microbiology
Antibodies
Virus
Lymphatic System
03 medical and health sciences
Diagnostic Medicine
In vivo
Virology
Retroviruses
Fluorescence Imaging
Genetics
medicine
Animals
Distribution (pharmacology)
Microbial Pathogens
Molecular Biology
030304 developmental biology
PET-CT
Mucous Membrane
Lentivirus
Organisms
Biology and Life Sciences
HIV
Proteins
RC581-607
Macaca mulatta
Gastrointestinal Tract
Immunoglobulin A, Secretory
biology.protein
Parasitology
Lymph Nodes
Immunologic diseases. Allergy
Digestive System
Positron Emission Tomography
Neuroscience
030215 immunology
Subjects
Details
- Language :
- English
- ISSN :
- 15537374 and 15537366
- Volume :
- 17
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- PLoS Pathogens
- Accession number :
- edsair.doi.dedup.....e15cb5f5661d494210cc2e8472676fd8