Prostaglandin A1 triggers Mayaro virus inhibition and heat shock protein 70 expression in an epithelial cell model

Abstract

Introduction: The Mayaro virus (MAYV), which is an arbovirus closely related to the Chikungunya virus, causes a dengue-like acute illness that is endemic to Central and South America. We investigated the anti-MAYV activity of prostaglandin A 1 (PGA 1), a hormone which exhibits antiviral activity against both ribonucleic acid (RNA) and deoxyribonucleic acid (DNA) viruses. Further, we examined the effects of inducting the stress protein HSP70 following PGA 1 treatment. Methods: Hep-2 cells infected with MAYV were treated with PGA 1 (0.1-6μg/ml) 12h before infection and for different periods post-infection. Inhibition of viral replication inhibition was analyzed via viral titer determination, whereas the effect of PGA 1 on viral morphogenesis was examined via transmission electron microscopy (TEM). Autoradiography (with 35 S methionine labeling) and western blotting were used to assess the effect of PGA 1 treatment on viral and cellular protein synthesis, and on HSP70 induction, respectively. Results: PGA 1 strongly reduced viral replication in Hep-2 cells, particularly when added during the early stages of viral replication. Although PGA 1 treatment inhibited viral replication by 95% at 24 hours post-infection (hpi), viral structural protein synthesis was inhibited only by 15%. TEM analysis suggested that PGA 1 inhibited replication before viral morphogenesis. Western blot and densitometry analyses showed that PGA 1 treatment increased HSP70 protein levels, although this was not detectable via autoradiography. Conclusions: PGA 1 inhibits MAYV replication in Hep-2 cells at early stages of viral replication, prior to production of viral structural proteins, possibly via HSP70 induction.

Mayaro Virus Replication Restriction and Induction of Muscular Inflammation in Mice Are Dependent on Age, Type-I Interferon Response, and Adaptive Immunity

“…The muscular tropism and damage could correlate with the main clinical symptoms observed in MAYV and is characteristic of myositis induced by other arthritogenic Alphavirus (Tesh et al, 1999; Ng, 2017). Currently, few studies investigated cellular tropism and consequences of MAYV replication (Cavalheiro et al, 2016; Camini et al, 2017; Caldas et al, 2018; Danillo Lucas Alves and Benedito Antonio Lopes da, 2018). It was demonstrated that MAYV replicates in RAW macrophages in vitro , promoting an increase in the amounts of reactive oxygen species and TNF (Cavalheiro et al, 2016).…”

Mayaro virus replication restriction and induction of muscular inflammation in mice are dependent on age and type-I interferon response

“…The muscular tropism and damage could correlate with the main clinical symptoms observed in MAYV and is characteristic of myositis induced by other arthritogenic Alphavirus (12,40). Currently, few studies investigated cellular tropism and consequences of MAYV replication (21,(41)(42)(43). It was demonstrated that MAYV replicates in RAW macrophages in vitro, promoting an increase in the amounts of reactive oxygen species and TNF (43).…”

An update on the development of antiviral against Mayaro virus: from molecules to potential viral targets

“…Some of the first natural molecules tested for their potential to inhibit MAYV replication in vitro were Prostaglandin A1 (PGA1) and Prostaglandin B2 (PGB2) (Ishimaru et al 1998 ). PGA1, a natural molecule that possesses a hormone-like lipid structure, is produced by cells in the presence of injury and/or inflammation (Caldas et al 2018 ). Alternatively, PGB2 is a lipid mediator that acts as an auxiliary signal to T lymphocyte activation (Ishimaru et al 1998 ; Raulin 2002 ).…”