Infectivity of three Mayaro Virus (Genus Alphavirus, Family Togaviridae) geographic isolates in human cell lines

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 that this virus could further expand its geographic range. Given the potential importance of this pathogen, we sought to fill some 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. MAYV strain isolated from Bolivia (MAYV-U) infected cells more rapidly compared to MAYV strains isolated in Peru and Brazil (MAYV-P; MAYV-B), with high titers (1x108 pfu/ml) peaking at 37 hours post infection. MAYV-U also caused the most cytopathic effect in a time dependent manner. Furthermore, differently from the other two prototypic strains, MAYV-U harbors unique mutations in the E2 protein, D60G and S205F, likely to interact with the host cell receptor, which may explain the observed differences in infectivity. We further demonstrate that pre-treatment of cells with interferon-{beta} 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 MAYV phenotypic variation according to geography. Author SummaryArthropod-borne viruses are of great public health concern, causing epidemics worldwide due to climate change, changes in land use, rapid urbanization, and the expanding geographic ranges of suitable vectors. Among these viruses, Mayaro is an emerging virus for which little is currently known. This study aims to answer fundamental questions of Mayaro virus biology using three geographically distinct viral strains to examine variability in infection kinetics and infectivity in susceptible cell types. We found one geographic isolate to have accelerated infection kinetics and increased cell damage because of infection. To better understand what was unique about this isolate, we compared their envelope protein, which is critical for entry into a cell. We found that the isolate with increased replication kinetics possessed mutations at sites that may promote viral entry, which could explain these findings. Together, these findings further our understanding of Mayaro virus biology and provide insight into factors that contribute to Mayaro transmission and infectivity.