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Infectivity of three Mayaro Virus geographic isolates in human cell lines
Aum R Patel1, Melissa Dulcey2, Nabil Abid3
1Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, USA.
Abstract:
Mayaro virus (MAYV) is an emergent arthropod-borne virus that causes an acute febrile illness accompanied by arthralgia, similar to chikungunya virus. Increasing urbanization of MAYV outbreaks in the Americas has led to concerns for geographic expansion and spillover. Given the potential importance of this pathogen, we sought to fill critical gaps in knowledge regarding MAYV infectivity and geographic variation. This study describes the cytopathogenicity of MAYV in human dermal fibroblasts, human skeletal muscle satellite cells, human embryonic kidney cells (HEK), peripherally derived human macrophages, and Vero cells. We found that regional differences between these viruses do not affect replication kinetics, with high titers peaking at 37 h post infection. MAYV-U, did however, cause the most cytopathic effect in a time-dependent manner. Compared to the other two prototypic isolates, MAYV-U harbors unique mutations in the E2 protein, D60G and S205F, that are likely to interact with the host cell receptor and could affect infectivity. We further demonstrate that pre-treatment of cells with interferon-β inhibited viral replication in a dose-dependent manner. Together, these findings advance our understanding of MAYV infection of human target cells and provide initial data regarding variation according to geography.
Insights
Mayaro virus (MAYV) causes febrile illness. This study shows regional MAYV strains replicate similarly, but one strain exhibits unique mutations affecting cell damage and infectivity.
Area of Science:
- Virology
- Pathogen research
- Emerging infectious diseases
Background:
- Mayaro virus (MAYV) is an emergent arthropod-borne virus causing febrile illness and arthralgia.
- Urbanization of MAYV outbreaks raises concerns for geographic expansion and spillover.
- Knowledge gaps exist regarding MAYV infectivity and geographic variation.
Purpose of the Study:
- To investigate the cytopathogenicity of MAYV in various human cell types.
- To analyze the impact of geographic origin on MAYV replication and virulence.
- To identify potential viral factors influencing infectivity.
Main Methods:
- Assessed MAYV cytopathogenicity in human dermal fibroblasts, skeletal muscle satellite cells, HEK cells, macrophages, and Vero cells.
- Compared replication kinetics and viral titers across different MAYV isolates.
- Analyzed genetic variations, specifically mutations in the E2 protein (D60G, S205F) of the MAYV-U strain.
- Investigated the effect of interferon-β pre-treatment on viral replication.
Main Results:
- MAYV isolates showed similar replication kinetics, with peak titers at 37 hours post-infection.
- The MAYV-U strain demonstrated the most significant time-dependent cytopathic effect.
- Unique E2 protein mutations (D60G, S205F) in MAYV-U were identified, potentially affecting host cell receptor interaction and infectivity.
- Interferon-β inhibited MAYV replication in a dose-dependent manner.
Conclusions:
- Geographic origin does not significantly alter MAYV replication rates in tested cell lines.
- Specific E2 protein mutations in MAYV-U may contribute to its enhanced cytopathic effect and infectivity.
- Interferon-β is a potential factor in controlling MAYV infection.
- Findings advance understanding of MAYV cell tropism and geographic variation.
