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

Abstract

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.