Mayaro Virus Infects Human Brain Cells and Induces a Potent Antiviral Response in Human Astrocytes.

Michèle Bengue,Julien Pompon,Jonathan Barthelemy,Yannick Simonin,Xavier De Lamballerie,Pauline Ferraris,Sara Salinas,Florian Liégeois,Antoine Nougairède,Cheikh Tidiane Diagne,Rodolphe Hamel,Dorothée Missé

doi:10.3390/v13030465

Abstract

Mayaro virus (MAYV) and chikungunya virus (CHIKV) are known for their arthrotropism, but accumulating evidence shows that CHIKV infections are occasionally associated with serious neurological complications. However, little is known about the capacity of MAYV to invade the central nervous system (CNS). We show that human neural progenitors (hNPCs), pericytes and astrocytes are susceptible to MAYV infection, resulting in the production of infectious viral particles. In primary astrocytes, MAYV, and to a lesser extent CHIKV, elicited a strong antiviral response, as demonstrated by an increased expression of several interferon-stimulated genes, including ISG15, MX1 and OAS2. Infection with either virus led to an enhanced expression of inflammatory chemokines, such as CCL5, CXCL10 and CXCL11, whereas MAYV induced higher levels of IL-6, IL-12 and IL-15 in these cells. Moreover, MAYV was more susceptible than CHIKV to the antiviral effects of both type I and type II interferons. Taken together, this study shows that although MAYV and CHIKV are phylogenetically related, they induce different types of antiviral responses in astrocytes. This work is the first to evaluate the potential neurotropism of MAYV and shows that brain cells and particularly astrocytes and hNPCs are permissive to MAYV, which, consequently, could lead to MAYV-induced neuropathology.

Highlights

Arthropod-borne viruses have been identified in all continents as emerging and re-emerging etiologic agents, causing illness in humans and domestic animals, thereby becoming a serious challenge to public health [1]
To better characterize the neurovirulence of Mayaro virus (MAYV), and compare it to chikungunya virus (CHIKV), we evaluated the ability of both viruses to infect human brain cells, including neural progenitors, pericytes and astrocytes, that mediate early antiviral responses to pathogens invading the central nervous system (CNS) [35]
To evaluate and compare MAYV and CHIKV replication efficiency in human brain cells, hNPCs, primary astrocytes and pericytes were infected with either virus at multiplicity of infection (MOI) 5

Summary

Introduction

Arthropod-borne viruses have been identified in all continents as emerging and re-emerging etiologic agents, causing illness in humans and domestic animals, thereby becoming a serious challenge to public health [1] The emergence of these viruses and their epidemic potential is thought to be favored by environmental factors, international travels, urban development, in addition to climate and ecological changes along with the spread of vectors and reservoirs [2]. Amongst several others potential vectors, the major anthropophilic urban mosquitoes (Aedes aegypti and Aedes albopictus) and some Anopheles species have been shown to be able to transmit MAYV [4,5,6] It was first identified in 1954 from rural workers in Trinidad and Tobago and thought to be limited to the South American continent causing sporadic outbreaks next to the forest environment [7,8]. An epidemiological alert was announced by the Pan American Health Organization in 2019 due to the rise in outbreaks and the plasticity of the virus [11]

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