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- Title
Mayaro virus pathogenesis and immunity in rhesus macaques.
- Authors
Weber, Whitney C.; Labriola, Caralyn S.; Kreklywich, Craig N.; Ray, Karina; Haese, Nicole N.; Andoh, Takeshi F.; Denton, Michael; Medica, Samuel; Streblow, Magdalene M.; Smith, Patricia P.; Mizuno, Nobuyo; Frias, Nina; Fisher, Miranda B.; Barber-Axthelm, Aaron M.; Chun, Kimberly; Uttke, Samantha; Whitcomb, Danika; DeFilippis, Victor; Rakshe, Shauna; Fei, Suzanne S.
- 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. Author summary: Mayaro virus (MAYV) is an arbovirus capable of causing debilitating arthritis and myalgia in humans and the virus is currently circulating in Central and South America. With several factors supporting viral emergence, MAYV is a public health risk due to the lack of FDA-approved countermeasures. Although non-human primate (NHP) infection models are well established for chikungunya virus (CHIKV) and the equine encephalitic alphaviruses, there is currently no well-characterized NHP model of MAYV pathogenesis. With evidence of well-established mouse models of MAYV infection and a report from 1967 demonstrating that MAYV infection of NHPs in a laboratory setting was feasible, we aimed to further characterize MAYV infection in three rhesus macaques. Following precursor studies in mice to identify an optimal viral strain for NHP infection, we subcutaneously challenged rhesus macaques and characterized viral pathogenesis and immunity over the course of 10 days. Our study establishes a framework for future evaluation of MAYV-specific treatments in this relevant animal model.
- Subjects
RHESUS monkeys; UNITED States. Food &; Drug Administration; ALPHAVIRUS diseases; LABORATORY infections; PERIPHERAL nervous system; ALPHAVIRUSES; CHIKUNGUNYA virus; LYMPHOID tissue
- Publication
PLoS Neglected Tropical Diseases, 2023, Vol 17, Issue 11, p1
- ISSN
1935-2727
- Publication type
Article
- DOI
10.1371/journal.pntd.0011742