Cell-to-Cell Contact and Nectin-4 Govern Spread of Measles Virus from Primary Human Myeloid Cells to Primary Human Airway Epithelial Cells
| Autor: | Anna C. Mark, Ni Li, Brajesh K. Singh, Mathieu Mateo, Roberto Cattaneo, Patrick L. Sinn |
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| Přispěvatelé: | Department of Molecular Medicine and Virology and Gene Therapy Graduate Track, Mayo Clinic [Rochester] |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
MESH: Virus Internalization Respiratory System Cell Cell Fusion Myeloid Cells Cells Cultured MESH: Respiratory System Cell fusion biology MESH: Dendritic Cells Cell adhesion molecule MESH: Nectins Virus-Cell Interactions 3. Good health medicine.anatomical_structure MESH: Epithelial Cells [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology MESH: Cell Adhesion Molecules MESH: Measles Receptors Virus MESH: Cells Cultured Nectins 030106 microbiology Immunology Microbiology Virus Measles virus 03 medical and health sciences Immune system Virology medicine Humans MESH: Humans Macrophages MESH: Macrophages Epithelial Cells Dendritic Cells Virus Internalization biology.organism_classification MESH: Receptors Virus MESH: Myeloid Cells Epithelium 030104 developmental biology Insect Science MESH: Cell Fusion Respiratory epithelium Cell Adhesion Molecules MESH: Measles virus Measles |
| Zdroj: | Journal of Virology Journal of Virology, American Society for Microbiology, 2016, 90 (15), pp.6808-6817. ⟨10.1128/JVI.00266-16⟩ |
| ISSN: | 0022-538X 1098-5514 |
| DOI: | 10.1128/JVI.00266-16⟩ |
| Popis: | 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. IMPORTANCE Measles virus spreads rapidly and efficiently in human airway epithelial cells. This rapid spread is based on cell-to-cell contact rather than on particle release and reentry. Here we posit that MeV transfer from infected immune cells to epithelial cells also occurs by cell-to-cell contact rather than through cell-free particles. In addition, we sought to determine which immune cells transfer MeV infectivity to the human airway epithelium. Our studies are based on two types of human primary cells: (i) myeloid cells generated from donated blood and (ii) well-differentiated airway epithelial cells derived from donor lungs. We show that different types of myeloid cells, i.e., monocyte-derived macrophages and dendritic cells, transfer infection to airway epithelial cells. Furthermore, cell-to-cell contact is an important component of successful MeV transfer. Our studies elucidate a mechanism by which the most contagious human respiratory virus is delivered to the airway epithelium. |
| Databáze: | OpenAIRE |
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