[PMID]: | 26339044 |
[Au] Autor: | Pérez-Carmona N; Farré D; Martínez-Vicente P; Terhorst C; Engel P; Angulo A |
[Ad] Endereço: | Immunology Unit, Department of Cell Biology, Immunology, and Neurosciences, Medical School, University of Barcelona, Barcelona, Spain. |
[Ti] Título: | Signaling Lymphocytic Activation Molecule Family Receptor Homologs in New World Monkey Cytomegaloviruses. |
[So] Source: | J Virol;89(22):11323-36, 2015 Nov. |
[Is] ISSN: | 1098-5514 |
[Cp] País de publicação: | United States |
[La] Idioma: | eng |
[Ab] Resumo: | UNLABELLED: Throughout evolution, large DNA viruses have been usurping genes from their hosts to equip themselves with proteins that restrain host immune defenses. Signaling lymphocytic activation molecule (SLAM) family (SLAMF) receptors are involved in the regulation of both innate and adaptive immunity, which occurs upon engagement with their ligands via homotypic or heterotypic interactions. Here we report a total of seven SLAMF genes encoded by the genomes of two cytomegalovirus (CMV) species, squirrel monkey CMV (SMCMV) and owl monkey CMV (OMCMV), that infect New World monkeys. Our results indicate that host genes were captured by retrotranscription at different stages of the CMV-host coevolution. The most recent acquisition led to S1 in SMCMV. S1 is a SLAMF6 homolog with an amino acid sequence identity of 97% to SLAMF6 in its ligand-binding N-terminal Ig domain. We demonstrate that S1 is a cell surface glycoprotein capable of binding to host SLAMF6. Furthermore, the OMCMV genome encodes A33, an LY9 (SLAMF3) homolog, and A43, a CD48 (SLAMF2) homolog, two soluble glycoproteins which recognize their respective cellular counterreceptors and thus are likely to be viral SLAMF decoy receptors. In addition, distinct copies of further divergent CD48 homologs were found to be encoded by both CMV genomes. Remarkably, all these molecules display a number of unique features, including cytoplasmic tails lacking characteristic SLAMF signaling motifs. Taken together, our findings indicate a novel immune evasion mechanism in which incorporation of host SLAMF receptors that retain their ligand-binding properties enables viruses to interfere with SLAMF functions and to supply themselves with convenient structural molds for expanding their immunomodulatory repertoires. IMPORTANCE: The way in which viruses shape their genomes under the continual selective pressure exerted by the host immune system is central for their survival. Here, we report that New World monkey cytomegaloviruses have broadly captured and duplicated immune cell receptors of the signaling lymphocyte activation molecule (SLAM) family during host-virus coevolution. Notably, we demonstrate that several of these viral SLAMs exhibit exceptional preservation of their N-terminal immunoglobulin domains, which results in maintenance of their ligand-binding capacities. At the same time, these molecules present distinctive structural properties which include soluble forms and the absence of typical SLAM signaling motifs in their cytoplasmic domains, likely reflecting the evolutionary adaptation undergone to efficiently interfere with host SLAM family activities. The observation that the genomes of other large DNA viruses might bear SLAM family homologs further underscores the importance of these molecules as a novel class of immune regulators and as convenient scaffolds for viral evolution. |
[Mh] Termos MeSH primário: |
Antígenos CD/imunologia Aotidae/virologia Citomegalovirus/imunologia Ativação Linfocitária/imunologia Receptores de Superfície Celular/imunologia Saimiri/virologia
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[Mh] Termos MeSH secundário: |
Sequência de Aminoácidos Animais Antígenos CD/genética Antígenos CD/metabolismo Antígeno CD48 Infecções por Citomegalovirus/imunologia Infecções por Citomegalovirus/veterinária Infecções por Citomegalovirus/virologia Expressão Gênica/genética Regulação da Expressão Gênica/fisiologia Linfócitos/imunologia Glicoproteínas de Membrana/metabolismo Receptores de Superfície Celular/genética Receptores de Superfície Celular/metabolismo Transdução de Sinais/imunologia Membro 1 da Família de Moléculas de Sinalização da Ativação Linfocitária
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[Pt] Tipo de publicação: | JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T |
[Nm] Nome de substância:
| 0 (Antigens, CD); 0 (CD48 Antigen); 0 (Membrane Glycoproteins); 0 (Receptors, Cell Surface); 169535-43-7 (Signaling Lymphocytic Activation Molecule Family Member 1) |
[Em] Mês de entrada: | 1601 |
[Cu] Atualização por classe: | 170220 |
[Lr] Data última revisão:
| 170220 |
[Sb] Subgrupo de revista: | IM |
[Da] Data de entrada para processamento: | 150905 |
[St] Status: | MEDLINE |
[do] DOI: | 10.1128/JVI.01296-15 |
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