Different Roles of the Three Loops Forming the Adhesive Interface of Nectin-4 in Measles Virus Binding and Cell Entry, Nectin-4 Homodimerization, and Heterodimerization with Nectin-1
| Autor: | Justin W. Maroun, Chanakha K. Navaratnarajah, Patrick L. Sinn, Roberto Cattaneo, Marc Lopez, Ianko D. Iankov, Mathieu Mateo, Robin C. Willenbring |
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| Přispěvatelé: | Department of Molecular Medicine and Virology and Gene Therapy Graduate Track, Mayo Clinic [Rochester], Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) |
| Rok vydání: | 2014 |
| Předmět: |
MESH: Virus Attachment
MESH: Virus Internalization Molecular Sequence Data Nectins Immunology MESH: Sequence Alignment Hemagglutinins Viral Virus Attachment Hemagglutinin (influenza) MESH: Amino Acid Sequence Microbiology Cell Line Measles virus Nectin Virology Animals Humans MESH: Animals Amino Acid Sequence Peptide sequence MESH: Humans MESH: Molecular Sequence Data biology MESH: Protein Multimerization Cell adhesion molecule RNA virus Virus Internalization MESH: Nectins biology.organism_classification MESH: Receptors Virus MESH: Cell Line Virus-Cell Interactions 3. Good health Cell biology Biochemistry Insect Science [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology MESH: Cell Adhesion Molecules biology.protein Receptors Virus Immunoglobulin superfamily Protein Multimerization MESH: Measles virus Cell Adhesion Molecules Sequence Alignment Poliovirus Receptor MESH: Hemagglutinins Viral |
| Zdroj: | Journal of Virology Journal of Virology, 2014, 88 (24), pp.14161-14171. ⟨10.1128/JVI.02379-14⟩ Journal of Virology, American Society for Microbiology, 2014, 88 (24), pp.14161-14171. ⟨10.1128/JVI.02379-14⟩ |
| ISSN: | 1098-5514 0022-538X |
| Popis: | Many viruses utilize cell adhesion molecules of the immunoglobulin superfamily as receptors. In particular, viruses of different classes exploit nectins. The large DNA viruses, herpes simplex and pseudorabies viruses, use ubiquitous nectins 1 and 2. The negative-strand RNA virus measles virus (MeV) uses tissue-specific nectin-4, and the positive-strand RNA virus poliovirus uses nectin-like 5 (necl-5), also known as poliovirus receptor. These viruses contact the BC, C′C″, and FG loops on the upper tip of their receptor's most membrane-distal domain. This location corresponds to the newly defined canonical adhesive interface of nectins, but how viruses utilize this interface has remained unclear. Here we show that the same key residues in the BC and FG loops of nectin-4 govern binding to the MeV attachment protein hemagglutinin (H) and cell entry, nectin-4 homodimerization, and heterodimerization with nectin-1. On the other hand, residues in the C′C″ loop necessary for homo- and heterotypic interactions are dispensable for MeV-induced fusion and cell entry. Remarkably, the C′C″ loop governs dissociation of the nectin-4 and H ectodomains. We provide formal proof that H can interfere with the formation of stable nectin-1/nectin-4 heterodimers. Finally, while developing an alternative model to study MeV spread, we observed that polarized primary pig airway epithelial sheets cannot be infected. We show that a single amino acid variant in the BC loop of pig nectin-4 fully accounts for restricted MeV entry. Thus, the three loops forming the adhesive interface of nectin-4 have different roles in supporting MeV H association and dissociation and MeV-induced fusion. IMPORTANCE Different viruses utilize nectins as receptors. Nectins are immunoglobulin superfamily glycoproteins that mediate cell-cell adhesion in vertebrate tissues. They interact through an adhesive interface located at the top of their membrane-distal domain. How viruses utilize the three loops forming this interface has remained unclear. We demonstrate that while nectin-nectin interactions require residues in all three loops, the association of nectin-4 with the measles virus hemagglutinin requires only the BC and FG loops. However, we discovered that residues in the C′C″ loop modulate the dissociation of nectin-4 from the viral hemagglutinin. Analogous mechanisms may support cell entry of other viruses that utilize nectins or other cell adhesion molecules of the immunoglobulin superfamily as receptors. |
| Databáze: | OpenAIRE |
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