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

Viruses. 2021 Mar 11;13(3):465. 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.

Keywords: alphavirus; arbovirus; astrocytes; chikungunya; mayaro; neural progenitors; neurotropism; pericytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2',5'-Oligoadenylate Synthetase / metabolism
  • Alphavirus / immunology*
  • Alphavirus Infections / immunology*
  • Alphavirus Infections / pathology
  • Animals
  • Astrocytes / immunology*
  • Astrocytes / virology*
  • Brain / immunology*
  • Brain / virology
  • Cell Line
  • Chemokine CCL5 / metabolism
  • Chemokine CXCL10 / metabolism
  • Chemokine CXCL11 / metabolism
  • Chikungunya Fever / immunology
  • Chikungunya virus / immunology
  • Chlorocebus aethiops
  • Cytokines / metabolism
  • Humans
  • Interferon Type I / immunology
  • Interferon-gamma / immunology
  • Myxovirus Resistance Proteins / metabolism
  • Neural Stem Cells / virology
  • Pericytes / virology
  • Ubiquitins / metabolism
  • Vero Cells

Substances

  • CCL5 protein, human
  • CXCL10 protein, human
  • CXCL11 protein, human
  • Chemokine CCL5
  • Chemokine CXCL10
  • Chemokine CXCL11
  • Cytokines
  • Interferon Type I
  • MX1 protein, human
  • Myxovirus Resistance Proteins
  • Ubiquitins
  • ISG15 protein, human
  • Interferon-gamma
  • OAS2 protein, human
  • 2',5'-Oligoadenylate Synthetase