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Mechanistic basis of post-treatment control of SIV after anti-α4β7 antibody therapy
- Source :
- PLoS Computational Biology, Vol 17, Iss 6, p e1009031 (2021), PLoS Computational Biology
- Publication Year :
- 2021
- Publisher :
- Public Library of Science (PLoS), 2021.
-
Abstract
- Treating macaques with an anti-α4β7 antibody under the umbrella of combination antiretroviral therapy (cART) during early SIV infection can lead to viral remission, with viral loads maintained at < 50 SIV RNA copies/ml after removal of all treatment in a subset of animals. Depletion of CD8+ lymphocytes in controllers resulted in transient recrudescence of viremia, suggesting that the combination of cART and anti-α4β7 antibody treatment led to a state where ongoing immune responses kept the virus undetectable in the absence of treatment. A previous mathematical model of HIV infection and cART incorporates immune effector cell responses and exhibits the property of two different viral load set-points. While the lower set-point could correspond to the attainment of long-term viral remission, attaining the higher set-point may be the result of viral rebound. Here we expand that model to include possible mechanisms of action of an anti-α4β7 antibody operating in these treated animals. We show that the model can fit the longitudinal viral load data from both IgG control and anti-α4β7 antibody treated macaques, suggesting explanations for the viral control associated with cART and an anti-α4β7 antibody treatment. This effective perturbation to the virus-host interaction can also explain observations in other nonhuman primate experiments in which cART and immunotherapy have led to post-treatment control or resetting of the viral load set-point. Interestingly, because the viral kinetics in the various treated animals differed—some animals exhibited large fluctuations in viral load after cART cessation—the model suggests that anti-α4β7 treatment could act by different primary mechanisms in different animals and still lead to post-treatment viral control. This outcome is nonetheless in accordance with a model with two stable viral load set-points, in which therapy can perturb the system from one set-point to a lower one through different biological mechanisms.<br />Author summary Some macaques treated with an anti-α4β7 monoclonal antibody along with antiretroviral therapy during the early stages of simian immunodeficiency virus infection had their viral load become undetectable (below 50 SIV RNA copies/ml) after all treatment was stopped, whereas animals not given the antibody all had their viral loads rebound to high levels. Using a mathematical model, we examined four potential ways in which the antibody could have altered the balance between viral growth and immune control to maintain an undetectable viral load. We show that a shift to controlled infection can occur through multiple biologically reasonable mechanisms of action of the anti-α4β7 antibody.
- Subjects :
- RNA viruses
0301 basic medicine
Integrins
Physiology
viruses
medicine.medical_treatment
Cancer Treatment
Simian Acquired Immunodeficiency Syndrome
Monkeys
CD8-Positive T-Lymphocytes
Pathology and Laboratory Medicine
Biochemistry
White Blood Cells
0302 clinical medicine
Immunodeficiency Viruses
Animal Cells
Immune Physiology
Medicine and Health Sciences
Biology (General)
Mammals
Immune System Proteins
Ecology
biology
T Cells
Eukaryota
Antibodies, Monoclonal
Viral Load
Combined Modality Therapy
SIV
Oncology
Computational Theory and Mathematics
Medical Microbiology
Viral Pathogens
Modeling and Simulation
Vertebrates
Viruses
Simian Immunodeficiency Virus
Viral Clearance
Pathogens
Cellular Types
Antibody
Viral load
Macaque
Research Article
Primates
Cart
QH301-705.5
Immune Cells
Immunology
Antigen-Presenting Cells
Viremia
Microbiology
Antiviral Agents
Antibodies
Lymphocyte Depletion
Virus
03 medical and health sciences
Cellular and Molecular Neuroscience
Immune system
Antibody Therapy
Virology
Old World monkeys
Retroviruses
Genetics
medicine
Animals
Microbial Pathogens
Molecular Biology
Ecology, Evolution, Behavior and Systematics
Blood Cells
Biology and life sciences
Lentivirus
Organisms
Proteins
Cell Biology
Immunotherapy
medicine.disease
030104 developmental biology
Amniotes
biology.protein
Macaca
Clinical Immunology
Clinical Medicine
Zoology
Viral Transmission and Infection
030217 neurology & neurosurgery
CD8
Subjects
Details
- ISSN :
- 15537358
- Volume :
- 17
- Database :
- OpenAIRE
- Journal :
- PLOS Computational Biology
- Accession number :
- edsair.doi.dedup.....cc99d9c556ba5858df4b69ef7ed446d8