Cell-to-cell contact and nectin-4 govern spread of measles virus from primary human myeloid cells to primary human airway epithelial cells

Brajesh K. Singh, Ni Li, Anna C. Mark, Mathieu Mateo, Roberto Cattaneo, Patrick L. Sinna

Research output: Contribution to journalArticle

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Abstract

Measles is a highly contagious, acute viral illness. Immune cells within the airways are likely first targets of infection, and these cells traffic measles virus (MeV) to lymph nodes for amplification and subsequent systemic dissemination. Infected immune cells are thought to return MeV to the airways; however, the mechanisms responsible for virus transfer to pulmonary epithelial cells are poorly understood. To investigate this process, we collected blood from human donors and generated primary myeloid cells, specifically, monocyte-derived macrophages (MDMs) and dendritic cells (DCs). MDMs and DCs were infected with MeV and then applied to primary cultures of well-differentiated airway epithelial cells from human donors (HAE). Consistent with previous results obtained with free virus, infected MDMs or DCs were incapable of transferring MeV to HAE when applied to the apical surface. Likewise, infected MDMs or DCs applied to the basolateral surface of HAE grown on small-pore (0.4-μm) support membranes did not transfer virus. In contrast, infected MDMs and DCs applied to the basolateral surface of HAE grown on large-pore (3.0-μm) membranes successfully transferred MeV. Confocal microscopy demonstrated that MDMs and DCs are capable of penetrating large-pore membranes but not small-pore membranes. Further, by using a nectin-4 blocking antibody or recombinant MeV unable to enter cells through nectin-4, we demonstrated formally that transfer from immune cells to HAE occurs in a nectin-4-dependent manner. Thus, both infected MDMs and DCs rely on cell-to-cell contacts and nectin-4 to efficiently deliver MeV to the basolateral surface of HAE.

Original languageEnglish (US)
Pages (from-to)6808-6817
Number of pages10
JournalJournal of Virology
Volume90
Issue number15
DOIs
StatePublished - 2016

Fingerprint

Measles virus
Myeloid Cells
Dendritic Cells
dendritic cells
monocytes
epithelial cells
Epithelial Cells
Macrophages
macrophages
cells
Membranes
Viruses
viruses
Blocking Antibodies
Measles
nectins
Blood Donors
Confocal Microscopy
traffic
lymph nodes

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)
  • Virology

Cite this

Cell-to-cell contact and nectin-4 govern spread of measles virus from primary human myeloid cells to primary human airway epithelial cells. / Singh, Brajesh K.; Li, Ni; Mark, Anna C.; Mateo, Mathieu; Cattaneo, Roberto; Sinna, Patrick L.

In: Journal of Virology, Vol. 90, No. 15, 2016, p. 6808-6817.

Research output: Contribution to journalArticle

Singh, Brajesh K. ; Li, Ni ; Mark, Anna C. ; Mateo, Mathieu ; Cattaneo, Roberto ; Sinna, Patrick L. / Cell-to-cell contact and nectin-4 govern spread of measles virus from primary human myeloid cells to primary human airway epithelial cells. In: Journal of Virology. 2016 ; Vol. 90, No. 15. pp. 6808-6817.
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