tetano
Editor, Senior Moderator
J Virol. 2012 Jul 25. [Epub ahead of print]
The virus entry of influenza A virus with a α2,6-linked sialic acid binding preference requires host fibronectin.
Leung HS, Li OT, Chan RW, Chan MC, Nicholls JM, Poon LL.
Source
State Key Laboratory for Emerging Infectious Diseases, Centre of Influenza Research and School of Public Health, The University of Hong Kong.
Abstract
The receptor binding specificity of influenza A virus is one of the major determinants of viral tropism and host specificity. In general, avian viral hemagglutinin prefers to bind to α2,3-linked sialic acid, whereas the human viral hemagglutinin prefers to bind to α2,6-linked sialic acid. Here, we demonstrate that host fibronectin protein plays an important role in the lifecycle of some influenza A viruses. Treating cells with anti-fibronectin antibodies or fibronectin-specific siRNA can inhibit the virus replication of human H1N1 influenza A viruses. Strikingly, these inhibitory effects cannot be observed in cells infected with H5N1 viruses. By using reverse genetics techniques, we observe that the receptor binding specificity, but not the origin of hemagglutinin subtype, is responsible for this differential inhibitory effect. Changing the binding preference of hemagglutinin from α2,6-linked sialic acid to α2,3-linked sialic acid can make the virus resistant to the anti-fibronectin antibody treatment, and vice versa. Our further characterizations indicate that anti-fibronectin antibody acts on the early phase of viral replication cycle, but it has not effect on the initial binding of influenza A virus to cell surface. Our subsequent investigations further show that anti-FN antibody can block the post-attachment entry of influenza virus. Overall, these results suggest that sialic acid binding preference of influenza viral hemagglutinin can modulate the preferences of viral entry pathways, suggesting that there are subtle differences between the virus entries of human and avian influenza viruses.
PMID:
22837202
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/22837202
The virus entry of influenza A virus with a α2,6-linked sialic acid binding preference requires host fibronectin.
Leung HS, Li OT, Chan RW, Chan MC, Nicholls JM, Poon LL.
Source
State Key Laboratory for Emerging Infectious Diseases, Centre of Influenza Research and School of Public Health, The University of Hong Kong.
Abstract
The receptor binding specificity of influenza A virus is one of the major determinants of viral tropism and host specificity. In general, avian viral hemagglutinin prefers to bind to α2,3-linked sialic acid, whereas the human viral hemagglutinin prefers to bind to α2,6-linked sialic acid. Here, we demonstrate that host fibronectin protein plays an important role in the lifecycle of some influenza A viruses. Treating cells with anti-fibronectin antibodies or fibronectin-specific siRNA can inhibit the virus replication of human H1N1 influenza A viruses. Strikingly, these inhibitory effects cannot be observed in cells infected with H5N1 viruses. By using reverse genetics techniques, we observe that the receptor binding specificity, but not the origin of hemagglutinin subtype, is responsible for this differential inhibitory effect. Changing the binding preference of hemagglutinin from α2,6-linked sialic acid to α2,3-linked sialic acid can make the virus resistant to the anti-fibronectin antibody treatment, and vice versa. Our further characterizations indicate that anti-fibronectin antibody acts on the early phase of viral replication cycle, but it has not effect on the initial binding of influenza A virus to cell surface. Our subsequent investigations further show that anti-FN antibody can block the post-attachment entry of influenza virus. Overall, these results suggest that sialic acid binding preference of influenza viral hemagglutinin can modulate the preferences of viral entry pathways, suggesting that there are subtle differences between the virus entries of human and avian influenza viruses.
PMID:
22837202
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/22837202