T-cell immunoglobulin and mucin (TIM) contributes to the infection of human airway epithelial cells by pseudotype viruses containing Hantaan virus glycoproteins

Jennifer Mayor; Giulia Torriani; Sylvia Rothenberger; Olivier Engler

doi:10.1016/j.virol.2020.02.002

T-cell immunoglobulin and mucin (TIM) contributes to the infection of human airway epithelial cells by pseudotype viruses containing Hantaan virus glycoproteins

Virology. 2020 Apr:543:54-62. doi: 10.1016/j.virol.2020.02.002. Epub 2020 Feb 9.

Authors

Jennifer Mayor¹, Giulia Torriani², Sylvia Rothenberger³, Olivier Engler⁴

Affiliations

¹ Institute of Microbiology, University Hospital Center and University of Lausanne, Rue du Bugnon 48, CH-1011, Lausanne, Switzerland; Spiez Laboratory, CH-3700, Spiez, Switzerland.
² Institute of Microbiology, University Hospital Center and University of Lausanne, Rue du Bugnon 48, CH-1011, Lausanne, Switzerland.
³ Institute of Microbiology, University Hospital Center and University of Lausanne, Rue du Bugnon 48, CH-1011, Lausanne, Switzerland; Spiez Laboratory, CH-3700, Spiez, Switzerland. Electronic address: Sylvia.Rothenberger-Aubert@chuv.ch.
⁴ Spiez Laboratory, CH-3700, Spiez, Switzerland. Electronic address: olivier.engler@babs.admin.ch.

PMID: 32056847
DOI: 10.1016/j.virol.2020.02.002

Abstract

Hantaviruses are rodent-borne hemorrhagic fever viruses leading to serious diseases. Viral attachment and entry represent the first steps in virus transmission and are promising targets for antiviral therapeutic intervention. Here we investigated receptor use in human airway epithelium of the Old and New World hantaviruses Hantaan virus (HTNV) and Andes virus (ANDV). Using a biocontained recombinant vesicular stomatitis virus pseudotype platform, we provide first evidence for a role of the cellular phosphatidylserine (PS) receptors of the T-cell immunoglobulin and mucin (TIM) protein family in HTNV and ANDV infection. In line with previous studies, HTNV, but not ANDV, was able to use glycosaminoglycan heparan sulfate and α_vβ₃ integrin as co-receptors. In sum, our studies demonstrate for the first time that hantaviruses make use of apoptotic mimicry for infection of human airway epithelium, which may explain why these viruses can easily break the species barrier.

Keywords: Andes virus; Apoptotic mimicry; Axl; Hantaan virus; Hantavirus; Heparan sulfate; TIM-1.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Axl Receptor Tyrosine Kinase
Bacteriocins / pharmacology
Cell Line, Tumor
Epithelial Cells / metabolism
Epithelial Cells / virology
Hantaan virus / drug effects
Hantaan virus / metabolism*
Hantaan virus / pathogenicity
Hantaan virus / physiology
Haplorhini
Heparitin Sulfate / pharmacology
Hepatitis A Virus Cellular Receptor 1 / metabolism
Humans
Integrins / metabolism
Membrane Glycoproteins / metabolism*
Membrane Proteins / metabolism
Molecular Mimicry
Orthohantavirus / metabolism*
Orthohantavirus / physiology
Peptides / pharmacology
Proto-Oncogene Proteins / metabolism
Receptor Protein-Tyrosine Kinases / metabolism
Receptors, Cell Surface / metabolism*
Receptors, Virus / metabolism*
Respiratory Mucosa / metabolism
Respiratory Mucosa / virology*
Vesiculovirus / metabolism
Vesiculovirus / physiology
Viral Envelope Proteins / metabolism*

Substances

Bacteriocins
HAVCR1 protein, human
Hepatitis A Virus Cellular Receptor 1
Integrins
Membrane Glycoproteins
Membrane Proteins
Peptides
Proto-Oncogene Proteins
Receptors, Cell Surface
Receptors, Virus
TIMD4 protein, human
Viral Envelope Proteins
glycosaminoglycan receptor
phosphatidylserine receptor
duramycin
Heparitin Sulfate
Receptor Protein-Tyrosine Kinases
Axl Receptor Tyrosine Kinase