Biological Significance Of Amino Acids Deletion In NA Stalk Of H5N1 Avain Influenza Virus

The Neuraminidase(NA) of influenza A viruses, a classâ…¡glycoprotein with the amino terminus inside the cell and the carboxyl outside, is one of two major glycoproteins on the virus surface. The NA facilitates virus release from the host cell, preventing progeny viruses from self-aggregating. The NA protein is a tetramer with a box-shaped head comprising four coplanar and roughly spherical subunits, as well as centrally attached stalk with a hydrophobic region by which the stalk is embedded in the viral membrane. The enzymatic domain of the NA is held away from the virus envelope by a polypeptide stalk of variable length. The number and sequence of amino acids residues in the stalk region vary considerably among different viruses, even within the same subtypes.It has been reported that NA gene of some H1N1 influenza A virus strains isolated since 1933 is characterized by a deletion of 11 to 16 amino acids in the stalk. The spontaneous mutant in NA stalk of H1N1 virus lacks enzyme activity with large substrate (fetuin) but not with small substrate (sialyllactose). Recently, NA genes of some H5N1 virus also have been found the same unique mutation in the stalk, a deletion of 15 to 20 amino acids. However,biological significance of this mutation has not yet been reported.In order to investigate biological significance of the amino acids deletion in NA stalk of H5N1, five reassorted H5N1/PR8 viruses named 506, m506-, 646, m646+ and 196 were generated via eight-plasmid based reverse genetics system. The six internal genes...