Mayaro virus infection elicits a robust pro-inflammatory and antiviral response in human macrophages.

Autor: Hernández-Sarmiento LJ; Grupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia UdeA, Calle 70 No. 52-21, Medellín, Colombia., Tamayo-Molina YS; Grupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia UdeA, Calle 70 No. 52-21, Medellín, Colombia., Valdés-López JF; Grupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia UdeA, Calle 70 No. 52-21, Medellín, Colombia., Urcuqui-Inchima S; Grupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia UdeA, Calle 70 No. 52-21, Medellín, Colombia. Electronic address: silvio.urcuqui@udea.edu.co.
Jazyk: angličtina
Zdroj: Acta tropica [Acta Trop] 2024 Apr; Vol. 252, pp. 107146. Date of Electronic Publication: 2024 Feb 09.
DOI: 10.1016/j.actatropica.2024.107146
Abstrakt: Mayaro virus (MAYV), the etiological agent of Mayaro fever (MAYF), is an emergent arbovirus pathogen belonging to Togaviridae family. MAYF is characterized by high inflammatory component that can cause long-lasting arthralgia that persists for months. Macrophages are viral targets and reservoirs, key components of innate immunity and host response. Given the importance of this pathogen, our aim was to determine the inflammatory and antiviral response of human monocyte-derived macrophages (MDMs) infected with MAYV. First, we established the replication kinetics of the virus. Thereafter, we determined the expression of pattern recognition receptors, NF-ĸB complex, interferons (IFNs), two interleukin 27 (IL27) subunits, IFN-stimulated genes (ISGs), and the production of cytokines/chemokines. We found that human MDMs are susceptible to MAYV infection in vitro, with a peak of viral particles released between 24- and 48-hours post-infection (h.p.i) at MOI 0.5, and between 12 and 24 h.p.i at MOI 1. Interestingly, we observed a significant decline in the production of infectious viral particles at 72 h.p.i that was associated with the induction of antiviral response and high cytotoxic effect of MAYV infection in MDMs. We observed modulation of several genes after MAYV infection, as well, we noted the activation of antiviral detection and response pathways (Toll-like receptors, RIG-I/MDA5, and PKR) at 48 h.p.i but not at 6 h.p.i. Furthermore, MAYV-infected macrophages express high levels of the three types of IFNs and the two IL27 subunits at 48 h.p.i. Moreover, we found higher production of IL6, IL1β, CXCL8/IL8, CCL2, and CCL5 at 48 h.p.i as compared to 6 h.p.i. A robust antiviral response (ISG15, APOBEC3A, IFITM1, and MX2) was observed at 48 but not at 6 h.p.i. The innate and antiviral responses of MAYV-infected MDMs differ at 6 and 48 h.p.i. We conclude that MAYV infection induces robust pro-inflammatory and antiviral responses in human primary macrophages.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or conflict of interests that could have appeared to influence the work reported in this paper.
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Databáze: MEDLINE