tetano
Editor, Senior Moderator
J Virol. 2010 Dec 29. [Epub ahead of print]
N-linked Glycosylation Facilitates Sialic Acid-Independent Attachment and Entry of Influenza A Viruses into Cells Expressing DC-SIGN or L-SIGN.
Londrigan SL, Turville SG, Tate MD, Deng YM, Brooks AG, Reading PC.
The Department of Microbiology and Immunology, The University of Melbourne, 3010, Victoria, Australia; WHO Collaborating Centre for Reference and Research on Influenza, Victorian Infectious Diseases Reference Laboratory, North Melbourne, Victoria 3051, Australia; Westmead Millennium Institute, Sydney, NSW, Australia.
Abstract
It is widely recognized that sialic acid (SA) can mediate attachment of influenza virus to the cell surface, yet the specific receptors that mediate virus entry are not known. For many viruses, a definitive demonstration of receptor function has been achieved when non-permissive cells are rendered susceptible to infection following transfection of the gene encoding a putative receptor. For influenza virus, such approaches have been confounded by the abundance of SA on mammalian cells such that it has been difficult to identify cell lines that are not susceptible to infection. Herein, we have examined influenza virus infection of Lec2 Chinese Hamster Ovary (CHO) cells, a mutant cell line deficient in SA. Lec2 CHO cells were resistant to influenza virus infection and stable cell lines expressing either DC-SIGN or L-SIGN were generated to assess the potential of each molecule to function as SA-independent receptors for influenza A viruses. Virus strain BJx109 (H3N2) bound to Lec2 CHO cells expressing DC-SIGN or L-SIGN in a Ca(2+)-dependent manner and transfected cells were susceptible to virus infection. Treatment of Lec2-DC-SIGN and Lec2-L-SIGN cells with mannan, but not bacterial neuraminidase, blocked infection, consistent with SA-independent virus attachment and entry. Moreover, virus strain PR8 (H1N1) bears low levels of mannose-rich glycans and was inefficient at infecting Lec2 CHO cells expressing either DC-SIGN or L-SIGN whereas other glycosylated H1N1 subtype viruses could infect cells efficiently. Together, these data indicate that human C-type lectins (DC-SIGN and L-SIGN) can mediate attachment and entry of influenza viruses independently of cell-surface SA.
PMID: 21191006 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/21191006
N-linked Glycosylation Facilitates Sialic Acid-Independent Attachment and Entry of Influenza A Viruses into Cells Expressing DC-SIGN or L-SIGN.
Londrigan SL, Turville SG, Tate MD, Deng YM, Brooks AG, Reading PC.
The Department of Microbiology and Immunology, The University of Melbourne, 3010, Victoria, Australia; WHO Collaborating Centre for Reference and Research on Influenza, Victorian Infectious Diseases Reference Laboratory, North Melbourne, Victoria 3051, Australia; Westmead Millennium Institute, Sydney, NSW, Australia.
Abstract
It is widely recognized that sialic acid (SA) can mediate attachment of influenza virus to the cell surface, yet the specific receptors that mediate virus entry are not known. For many viruses, a definitive demonstration of receptor function has been achieved when non-permissive cells are rendered susceptible to infection following transfection of the gene encoding a putative receptor. For influenza virus, such approaches have been confounded by the abundance of SA on mammalian cells such that it has been difficult to identify cell lines that are not susceptible to infection. Herein, we have examined influenza virus infection of Lec2 Chinese Hamster Ovary (CHO) cells, a mutant cell line deficient in SA. Lec2 CHO cells were resistant to influenza virus infection and stable cell lines expressing either DC-SIGN or L-SIGN were generated to assess the potential of each molecule to function as SA-independent receptors for influenza A viruses. Virus strain BJx109 (H3N2) bound to Lec2 CHO cells expressing DC-SIGN or L-SIGN in a Ca(2+)-dependent manner and transfected cells were susceptible to virus infection. Treatment of Lec2-DC-SIGN and Lec2-L-SIGN cells with mannan, but not bacterial neuraminidase, blocked infection, consistent with SA-independent virus attachment and entry. Moreover, virus strain PR8 (H1N1) bears low levels of mannose-rich glycans and was inefficient at infecting Lec2 CHO cells expressing either DC-SIGN or L-SIGN whereas other glycosylated H1N1 subtype viruses could infect cells efficiently. Together, these data indicate that human C-type lectins (DC-SIGN and L-SIGN) can mediate attachment and entry of influenza viruses independently of cell-surface SA.
PMID: 21191006 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/21191006