Mayaro virus pathogenesis and immunity in rhesus macaques

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.; Axthelm, Michael K.; Smedley, Jeremy V.; Streblow, Daniel N.

doi:10.1371/journal.pntd.0011742

Cited by 3 publications

(1 citation statement)

References 133 publications

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“…RNAemia peaked at 2 dpi, with titres reaching 7.5Log 10 MAYV RNA ml −1 of plasma, and then waned rapidly, becoming nearly undetectable by RT-qPCR by 11 dpi. These kinetics closely recapitulate those observed in a recent MAYV challenge study of three rhesus macaques, in which animals were infected with 10 5 PFU virus [56] and compares with the proposed time course of human MAYV infection based on collated serological data from clinical cases [3]. Intravenous inoculation of cynomolgus macaques with CHIKV, considered a close evolutionary cousin of MAYV, also yields a similar curve in longitudinal RT-qPCR experiments [32].…”

Section: Discussionsupporting

confidence: 81%

Comparative pathogenesis of three Mayaro virus genotypes in the cynomolgus macaque

Hamilton,

Webb,

Peterson

et al. 2024

Journal of General Virology

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Mayaro virus (MAYV), a mosquito-borne alphavirus, is considered an emerging threat to public health with epidemic potential. Phylogenetic studies show the existence of three MAYV genotypes. In this study, we provide a preliminary analysis of the pathogenesis of all three MAYV genotypes in cynomolgus macaques (Macaca facicularis, Mauritian origin). Significant MAYV-specific RNAemia and viremia were detected during acute infection in animals challenged intravenously with the three MAYV genotypes, and strong neutralizing antibody responses were observed. MAYV RNA was detected at high levels in lymphoid tissues, joint muscle and synovia over 1 month after infection, suggesting that this model could serve as a promising tool in studying MAYV-induced chronic arthralgia, which can persist for years. Significant leucopenia was observed across all MAYV genotypes, peaking with RNAemia. Notable differences in the severity of acute RNAemia and composition of cytokine responses were observed among the three MAYV genotypes. Our model showed no outward signs of clinical disease, but several major endpoints for future MAYV pathology and intervention studies are described. Disruptions to normal blood cell counts and cytokine responses were markedly distinct from those observed in macaque models of CHIKV infection, underlining the importance of developing non-human primate models specific to MAYV infection.

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Section: Discussionsupporting

confidence: 81%

Comparative pathogenesis of three Mayaro virus genotypes in the cynomolgus macaque

Hamilton,

Webb,

Peterson

et al. 2024

Journal of General Virology

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Differential restriction of chikungunya virus in primary human cardiac endothelial cells occurs at multiple steps in the viral life cycle

Spector,

Noval,

Stapleford

2024

Preprint

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Arthropod-borne viruses (arboviruses) constitute a significant ongoing public health threat, as the mechanisms of pathogenesis remain incompletely understood. Cardiovascular symptomatology is emerging as an important manifestation of arboviral infection. We have recently studied the cardiac tropism and mechanisms implicated in cardiac damage in mice for the alphavirus chikungunya virus (CHIKV), and we therefore sought to evaluate the cardiac tropism of other emerging alphaviruses and arboviruses. Using human primary cardiac cells, we found that arboviruses from diverse viral families were able to replicate within these cells. Interestingly, we noted that while the closely related alphavirus Mayaro virus (MAYV) could replicate to high titers in primary human cardiac microvascular endothelial cells, pulmonary, and brain endothelial cells, the Indian Ocean Lineage of CHIKV (CHIKV-IOL) was completely restricted in all endothelial cells tested. Upon further investigation, we discovered that this restriction occurs at both entry and egress stages. Additionally, we observed that compared to CHIKV, MAYV may antagonize or evade the innate immune response more efficiently in human cardiac endothelial cells to increase infection. Overall, this study explores the tropism of arboviruses in human primary cardiac cells and characterizes the strain-specific restriction of CHIKV-IOL in human endothelial cells. Further work is needed to understand how the differential restriction of alphaviruses in human endothelial cells impacts pathogenesis in a living model, as well as the specific host factors responsible.Author SummaryMosquito-borne viruses, such as those within the alphavirus genus, are an ongoing concern to human health globally. While we have recently begun to explore the mechanisms of CHIKV-induced pathology in the heart, little is known about other arboviruses and alphaviruses related to CHIKV. Here, we identified that multiple cardiac cell types are susceptible to infection by several arboviruses important to public health. Specifically, we noted differences in how two related viruses, CHIKV and MAYV, infect endothelial cells from multiple origins. This work highlights the potential for other emerging arboviruses, in addition to CHIKV, to directly infect cardiac tissue. Moreover, it emphasizes the ability for MAYV, an emerging virus that is less studied, to infect various endothelial cell types to high titers, suggesting the need for further research on MAYV pathogenesis. Finally, this research identifies differences in infection between individual strains of CHIKV, suggesting a finely tuned mechanism of restriction in endothelial cells that can be further explored, as well as the need to study use different viral strains for future alphavirus research.

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Mayaro Virus: An Emerging Alphavirus in the Americas

Wei,

Tom,

Kim

2024

Viruses

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Mayaro virus (MAYV) is an arbovirus first isolated in Trinidad and Tobago in 1954. MAYV is the causative agent of Mayaro fever, which is characterised by high fever, maculopapular rash, myalgia and arthralgia. The potential for chronic arthralgia is of particular clinical concern. Currently, MAYV outbreaks are restricted to South and Central America, with some cases reported in Africa as well as several imported cases in Europe. However, in recent years, MAYV has become a growing global concern due to its potential to emerge into urban transmission cycles. Challenges faced with diagnostics, as well as a lack of specific antivirals or licensed vaccines further exacerbate the potential global health threat posed by MAYV. In this review, we discuss this emerging arboviral threat with a particular focus on the current treatment and vaccine development efforts. Overall, MAYV remains a neglected arbovirus due to its limited area of transmission. However, with the potential of its urbanisation and expanding circulation, the threat MAYV poses to global health cannot be overlooked. Further research into the improvement of current diagnostics, as well as the development of efficacious antivirals and vaccines will be crucial to help prevent and manage potential MAYV outbreaks.

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Mayaro virus pathogenesis and immunity in rhesus macaques

Cited by 3 publications

References 133 publications

Comparative pathogenesis of three Mayaro virus genotypes in the cynomolgus macaque

Comparative pathogenesis of three Mayaro virus genotypes in the cynomolgus macaque

Differential restriction of chikungunya virus in primary human cardiac endothelial cells occurs at multiple steps in the viral life cycle

Mayaro Virus: An Emerging Alphavirus in the Americas

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