Foot-and-mouth disease virus replicates only transiently in well-differentiated porcine nasal epithelial cells.
Three-dimensional (3D) porcine nasal mucosal and tracheal mucosal epithelial cell cultures were developed to analyze foot-and-mouth disease virus (FMDV) interactions with mucosal epithelial cells. The cells in these cultures differentiated and polarized until they closely resemble the epithelial layers seen in vivo. FMDV infected these cultures predominantly from the apical side, primarily by binding to integrin alphav beta6, in an Arg-Gly-Asp (RGD)-dependent manner. However, FMDV replicated only transiently without any visible cytopathic effect (CPE), and infectious progeny virus could be recovered only from the apical side. The infection induced the production of beta interferon (IFN-beta) and the IFN-inducible gene Mx1 mRNA, which coincided with the disappearance of viral RNA and progeny virus. The induction of IFN-beta mRNA correlated with the antiviral activity of the supernatants from both the apical and basolateral compartments. IFN-alpha mRNA was constitutively expressed in nasal mucosal epithelial cells in vitro and in vivo. In addition, FMDV infection induced interleukin 8 (IL-8) protein, granulocyte-macrophage colony-stimulating factor (GM-CSF), and RANTES mRNA in the infected epithelial cells, suggesting that it plays an important role in modulating the immune response.
Dash
Pradyot
P
Institute for Animal Health, Pirbright Laboratory, Pirbright, Woking, Surrey GU24 0NF, United Kingdom.
Barnett
Paul V
PV
Denyer
Michael S
MS
Jackson
Terry
T
Stirling
Catrina M A
CM
Hawes
Philippa C
PC
Simpson
Jennifer L
JL
Monaghan
Paul
P
Takamatsu
Haru-H
HH
D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism; D018946:Chemokine CCL5 / Q000096:biosynthesis; D003588:Cytopathogenic Effect, Viral; D004847:Epithelial Cells / Q000821:virology*; D005260:Female; D029544:Foot-and-Mouth Disease Virus / Q000276:immunology / Q000502:physiology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D016023:Integrins / Q000378:metabolism; D016898:Interferon-alpha / Q000096:biosynthesis; D016899:Interferon-beta / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D008297:Male; D009924:Organ Culture Techniques; D012333:RNA, Messenger / Q000096:biosynthesis; D020545:Respiratory Mucosa / Q000821:virology; D013552:Swine; D015533:Transcriptional Activation; D053585:Virus Attachment; D014779:Virus Replication
D000951:Antigens, Neoplasm; D018946:Chemokine CCL5; D016023:Integrins; D016898:Interferon-alpha; D016209:Interleukin-8; D012333:RNA, Messenger; C073878:integrin alphavbeta6; D016899:Interferon-beta; D016178:Granulocyte-Macrophage Colony-Stimulating Factor