Avian influenza viruses infect primary human bronchial epithelial cells unconstrained by sialic acid α2,3 residues.

Christine M Oshansky1 Jennifer A Pickens Konrad C Bradley Les P Jones Geraldine M Saavedra-Ebner James P Barber Jackelyn M Crabtree David A Steinhauer S Mark Tompkins Ralph A Tripp
Affiliations 1 institutions
  1. Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, Georgia, United States of America.

Abstract

Avian influenza viruses (AIV) are an important emerging threat to public health. It is thought that sialic acid (sia) receptors are barriers in cross-species transmission where the binding preferences of AIV and human influenza viruses are sias α2,3 versus α2,6, respectively. In this study, we show that a normal fully differentiated, primary human bronchial epithelial cell model is readily infected by low pathogenic H5N1, H5N2 and H5N3 AIV, which primarily bind to sia α2,3 moieties, and replicate in these cells independent of specific sias on the cell surface. NHBE cells treated with neuraminidase prior to infection are infected by AIV despite removal of sia α2,3 moieties. Following AIV infection, higher levels of IP-10 and RANTES are secreted compared to human influenza virus infection, indicating differential chemokine expression patterns, a feature that may contribute to differences in disease pathogenesis between avian and human influenza virus infections in humans.

Supporting text Virus Host Location
Adolescent 34 Animals 1948 Birds 212 Bronchi 6 Cell Differentiation 1 Cell Line 158 Chemokines 1 Cilia 1 Dogs 176 Epithelial Cells 27 Goblet Cells 1 Humans 1440 Influenza A virus 186 Influenza in Birds 341 Influenza, Human 286 Male 224 N-Acetylneuraminic Acid 25 Neuraminidase 62 Receptors, Cell Surface 28 Virus Replication 191 Virus Shedding 51 sialic acid receptor 14

Evidence records

3 total
Experimental Infection
3 records · 1 evidence types
Evidence type
3 records
OVE1020
Key finding

Low pathogenic H5N1 avian influenza virus infected and replicated in primary human bronchial epithelial cells in vitro.

Virus
Host
Location
Not specified
Supporting text

A normal fully differentiated, primary human bronchial epithelial cell model is readily infected by low pathogenic H5N1 AIV, which primarily binds to sia α2,3 moieties, and replicate in these cells independent of specific sias on the cell surface.

Method
in vitro infection assay | virus replication measurement
Sample type
bronchial epithelial cells
Experimental system
primary human bronchial epithelial cell culture model
OVE1021
Key finding

Low pathogenic H5N2 avian influenza virus infected and replicated in primary human bronchial epithelial cells in vitro.

Virus
Host
Location
Not specified
Supporting text

A normal fully differentiated, primary human bronchial epithelial cell model is readily infected by low pathogenic H5N2 AIV, which primarily binds to sia α2,3 moieties, and replicate in these cells independent of specific sias on the cell surface.

Method
in vitro infection assay | virus replication measurement
Sample type
bronchial epithelial cells
Experimental system
primary human bronchial epithelial cell culture model
OVE1022
Key finding

Low pathogenic H5N3 avian influenza virus infected and replicated in primary human bronchial epithelial cells in vitro.

Virus
Host
Location
Not specified
Supporting text

A normal fully differentiated, primary human bronchial epithelial cell model is readily infected by low pathogenic H5N3 AIV, which primarily binds to sia α2,3 moieties, and replicate in these cells independent of specific sias on the cell surface.

Method
in vitro infection assay | virus replication measurement
Sample type
bronchial epithelial cells
Experimental system
primary human bronchial epithelial cell culture model