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Analysis of Simian Immunodeficiency Virus-specific CD8+ T-cells in Rhesus Macaques by Peptide-MHC-I Tetramer Staining
Published on: December 23, 2016
Mayaro virus pathogenesis and immunity in rhesus macaques
Whitney C Weber1,2, Caralyn S Labriola1,3, Craig N Kreklywich1
1Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, Oregon, United States of America.
Abstract:
Mayaro virus (MAYV) is a mosquito-transmitted alphavirus that causes debilitating and persistent arthritogenic disease. While MAYV was previously reported to infect non-human primates (NHP), characterization of MAYV pathogenesis is currently lacking. Therefore, in this study we characterized MAYV infection and immunity in rhesus macaques. To inform the selection of a viral strain for NHP experiments, we evaluated five MAYV strains in C57BL/6 mice and showed that MAYV strain BeAr505411 induced robust tissue dissemination and disease. Three male rhesus macaques were subcutaneously challenged with 105 plaque-forming units of this strain into the arms. Peak plasma viremia occurred at 2 days post-infection (dpi). NHPs were taken to necropsy at 10 dpi to assess viral dissemination, which included the muscles and joints, lymphoid tissues, major organs, male reproductive tissues, as well as peripheral and central nervous system tissues. Histological examination demonstrated that MAYV infection was associated with appendicular joint and muscle inflammation as well as presence of perivascular inflammation in a wide variety of tissues. One animal developed a maculopapular rash and two NHP had viral RNA detected in upper torso skin samples, which was associated with the presence of perivascular and perifollicular lymphocytic aggregation. Analysis of longitudinal peripheral blood samples indicated a robust innate and adaptive immune activation, including the presence of anti-MAYV neutralizing antibodies with activity against related Una virus and chikungunya virus. Inflammatory cytokines and monocyte activation also peaked coincident with viremia, which was well supported by our transcriptomic analysis highlighting enrichment of interferon signaling and other antiviral processes at 2 days post MAYV infection. The rhesus macaque model of MAYV infection recapitulates many of the aspects of human infection and is poised to facilitate the evaluation of novel therapies and vaccines targeting this re-emerging virus.
Insights
Mayaro virus (MAYV) causes severe joint disease. This study used rhesus macaques to model MAYV infection, revealing viral spread, immune responses, and potential for vaccine development against this emerging alphavirus.
Area of Science:
- Virology
- Immunology
- Pathogenesis
Background:
- Mayaro virus (MAYV) is a mosquito-borne alphavirus causing persistent arthritogenic disease.
- Understanding MAYV pathogenesis in non-human primates (NHP) is crucial for developing effective interventions.
Purpose of the Study:
- To characterize MAYV infection and immune responses in a rhesus macaque model.
- To establish a relevant NHP model for evaluating MAYV therapies and vaccines.
Main Methods:
- Evaluated five MAYV strains in mice to select a virulent strain (BeAr505411).
- Inoculated three rhesus macaques with MAYV strain BeAr505411.
- Assessed viral dissemination, tissue pathology, and immune activation via necropsy and longitudinal blood sampling.
Main Results:
- Peak viremia occurred at 2 days post-infection (dpi), with viral RNA detected in muscles, joints, and various organs up to 10 dpi.
- Histopathology revealed joint and muscle inflammation, with skin lesions and lymphocytic aggregation in affected skin.
- Robust innate and adaptive immune activation, including neutralizing antibodies and elevated inflammatory cytokines, was observed.
Conclusions:
- The rhesus macaque model effectively recapitulates key aspects of human MAYV infection.
- This model provides a valuable platform for preclinical testing of novel MAYV vaccines and therapeutics.
- Findings highlight the potential for MAYV to cause widespread tissue dissemination and significant immune responses.
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