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DC-SIGN mediates avian H5N1 influenza virus infection in cis and in trans
Authors:Wang Sheng-Fan  Huang Jason C  Lee Yuan-Ming  Liu Shih-Jen  Chan Yu-Jiun  Chau Yat-Pang  Chong Pele  Chen Yi-Ming Arthur
Institution:a Department of Biotechnology and Laboratory Science in Medicine, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan;b AIDS Prevention and Research Center, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan;c Division of Preventive Medicine, Institute of Public Health, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan;d Division of Clinical Virology, Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, Taiwan;e Vaccine Research and Development Center, National Health Research Institutes, Taiwan;f Institute of Anatomy and Cell Biology, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan;g Division of Infectious Diseases, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan;h Department of Microbiology, School of Medicine, National Yang-Ming University, AIDS Prevention and Research Center, No. 155, Linong Street, Section 2, Taipei 112, Taiwan
Abstract:DC-SIGN, a C-type lectin receptor expressed in dendritic cells (DCs), has been identified as a receptor for human immunodeficiency virus type 1, hepatitis C virus, Ebola virus, cytomegalovirus, dengue virus, and the SARS coronavirus. We used H5N1 pseudotyped and reverse-genetics (RG) virus particles to study their ability to bind with DC-SIGN. Electronic microscopy and functional assay results indicate that pseudotyped viruses containing both HA and NA proteins express hemagglutination and are capable of infecting cells expressing α-2,3-linked sialic acid receptors. Results from a capture assay show that DC-SIGN-expressing cells (including B-THP-1/DC-SIGN and T-THP-1/DC-SIGN) and peripheral blood dendritic cells are capable of transferring H5N1 pseudotyped and RG virus particles to target cells; this action can be blocked by anti-DC-SIGN monoclonal antibodies. In summary, (a) DC-SIGN acts as a capture or attachment molecule for avian H5N1 virus, and (b) DC-SIGN mediates infections in cis and in trans.
Keywords:H5N1  DC-SIGN  Pseudotyped virus  Dendritic cells
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