Transcriptomic Analysis of Mayaro Virus-Infected Human Macrophages: Effects on Inflammatory and Antiviral Response

Lady Johana Hernández-Sarmiento Grupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia UdeA, Medellín, Colombia

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Y. S. Tamayo-Molina Grupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia UdeA, Medellín, Colombia

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Silvio Urcuqui-Inchima Grupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia UdeA, Medellín, Colombia

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Mayaro virus (MAYV) belongs to the Togaviridae family and is the etiologic agent of Mayaro fever, a disease in which inflammatory responses play a critical role in viral pathogenesis. Macrophages are targets of viral infection and key components of innate immunity and antiviral response. This study analyzed an RNA-sequencing (RNA-seq) dataset to gain insights into inflammatory and antiviral responses in monocyte-derived macrophages (MDMs) infected with the MAYV strain (Venezuelan 2010) at a multiplicity of infection (MOI) of 10. The RNA-seq results were validated by real-time quantitative polymerase chain reaction in MDMs infected with the MAYV strain from Brazil (MOI of 2). In addition, the replication capacity of MAYV and the resulting cell death in infected MDMs were assessed using plaque assays and flow cytometry. At 72 hours post-infection, transcriptomic analysis revealed that MAYV promotes a robust proinflammatory response by upregulating the expression of Toll-like receptors, RIG-I-like receptors, and the nuclear factor-κB complex. This strong inflammatory response was accompanied by a robust antiviral response dependent on type I/III interferon and interleukin-27. Both antiviral responses are mediated through the Janus kinase/signal transducer and activator of transcription signaling pathway, leading to the expression of interferon-stimulated genes. Moreover, MAYV-infected MDMs expressed markers of programmed cell death. These findings highlight the inflammatory response and antiviral activity of MDMs at a late stage in MAYV infection, suggesting a critical role of macrophages in MAYV pathogenesis.

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Author Notes

Financial support: This research was supported by Universidad de Antioquia-CODI (Grant no. Acta 2022-53011). The funders played no role in the study design or data collection.

Disclosures: The enrollment of individual participants and the collection of samples were carried out following the protocols approved by the Committee of Bioethics Research at Sede de Investigación Universitaria, Universidad de Antioquia (Medellín, Colombia). Before their involvement, all participants provided informed consent by signing a form according to the principles outlined in the Declaration of Helsinki. We declare that we have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Authors’ contributions: L. J. Hernández-Sarmiento and Y. S. Tamayo-Molina conceptualized the study. L. J. Hernández-Sarmiento and Y. S. Tamayo-Molina provided software. S. Urcuqui-Inchima provided resources. S. Urcuqui-Inchima acquired funding. L. J. Hernández-Sarmiento and Y. S. Tamayo-Molina performed formal analysis. L. J. Hernández-Sarmiento performed investigation. L. J. Hernández-Sarmiento and Y. S. Tamayo-Molina provided methodology. S. Urcuqui-Inchima provided visualization. S. Urcuqui-Inchima provided project administration. L. J. Hernández-Sarmiento wrote the original draft. L. J. Hernández-Sarmiento, Y. S. Tamayo-Molina, and S. Urcuqui-Inchima reviewed and edited the manuscript.

Current contact information: Lady Johana Hernández-Sarmiento, Y. S. Tamayo-Molina, and Silvio Urcuqui-Inchima, Universidad de Antioquia, Medellín, Colombia, E-mails: ladyj.hernandez@udea.edu.co, yordi.tamayo@udea.edu.co, and silvio.urcuqui@udea.edu.co.

Address correspondence to Silvio Urcuqui-Inchima, Grupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia UdeA, Calle 70 No. 52-21, Medellín 050010, Colombia. E-mail: silvio.urcuqui@udea.edu.co
 

 

 

 
 
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