Assuntos
Moléculas de Adesão Celular/fisiologia , Coronavirus Humano 229E/patogenicidade , Lectinas Tipo C/fisiologia , Receptores de Superfície Celular/fisiologia , Enzima de Conversão de Angiotensina 2 , Animais , Antígenos CD13/química , Células CHO , Moléculas de Adesão Celular/química , Linhagem Celular , Cricetinae , Células Dendríticas/virologia , Citometria de Fluxo , Humanos , Lectinas Tipo C/química , Camundongos , Peptidil Dipeptidase A/fisiologia , Ligação Proteica , Receptores de Superfície Celular/químicaRESUMO
Angiotensin-converting enzyme 2 (ACE2) is a receptor for SARS-CoV, the novel coronavirus that causes severe acute respiratory syndrome [Li, W. Moore, M. J., Vasilieva, N., Sui, J., Wong, S. K., Berne, M. A., Somasundaran, M., Sullivan, J. L., Luzuriaga, K., Greenough, T. C., et al. (2003) Nature 426, 450-454]. We have identified a different human cellular glycoprotein that can serve as an alternative receptor for SARS-CoV. A human lung cDNA library in vesicular stomatitis virus G pseudotyped retrovirus was transduced into Chinese hamster ovary cells, and the cells were sorted for binding of soluble SARS-CoV spike (S) glycoproteins, S(590) and S(1180). Clones of transduced cells that bound SARS-CoV S glycoprotein were inoculated with SARS-CoV, and increases in subgenomic viral RNA from 1-16 h or more were detected by multiplex RT-PCR in four cloned cell lines. Sequencing of the human lung cDNA inserts showed that each of the cloned cell lines contained cDNA that encoded human CD209L, a C-type lectin (also called L-SIGN). When the cDNA encoding CD209L from clone 2.27 was cloned and transfected into Chinese hamster ovary cells, the cells expressed human CD209L glycoprotein and became susceptible to infection with SARS-CoV. Immunohistochemistry showed that CD209L is expressed in human lung in type II alveolar cells and endothelial cells, both potential targets for SARS-CoV. Several other enveloped viruses including Ebola and Sindbis also use CD209L as a portal of entry, and HIV and hepatitis C virus can bind to CD209L on cell membranes but do not use it to mediate virus entry. Our data suggest that the large S glycoprotein of SARS-CoV may use both ACE2 and CD209L in virus infection and pathogenesis.
Assuntos
Proteínas de Ciclo Celular/fisiologia , Proteínas de Membrana/fisiologia , Receptores Virais/fisiologia , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/patogenicidade , Animais , Sequência de Bases , Células CHO , Proteínas de Ciclo Celular/genética , Linhagem Celular , Cricetinae , DNA Complementar/genética , Biblioteca Gênica , Humanos , Pulmão/metabolismo , Pulmão/virologia , Proteínas de Membrana/genética , Receptores de Coronavírus , Receptores Virais/genética , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/fisiologia , Transdução GenéticaRESUMO
In several mammalian species, including humans, coronavirus infection can modulate the host immune response. We show a potential role of dendritic cells (DC) in murine coronavirus-induced immune modulation and pathogenesis by demonstrating that the JAW SII DC line and primary DC from BALB/c mice and p/p mice with reduced expression of the murine coronavirus receptor, murine CEACAM1a, are susceptible to murine coronavirus infection by a receptor-dependent pathway.
Assuntos
Células Dendríticas/virologia , Glicoproteínas/fisiologia , Vírus da Hepatite Murina/patogenicidade , Receptores Virais/fisiologia , Animais , Antígenos CD , Antígeno CD11c/análise , Antígeno Carcinoembrionário , Moléculas de Adesão Celular , Linhagem Celular , Células Cultivadas , Camundongos , Camundongos Endogâmicos BALB C , Linfócitos T/imunologiaRESUMO
Truncated human coronavirus HCoV-229E spike glycoproteins containing amino acids 407 to 547 bound to purified, soluble virus receptor, human aminopeptidase N (hAPN). Soluble hAPN neutralized the infectivity of HCoV-229E virions at 37 degrees C, but not 4 degrees C. Binding of hAPN may therefore trigger conformational changes in the viral spike protein at 37 degrees C that facilitate virus entry.
