DETERMINING THE ABILITY OF H5N1 TO MEDIATE ENTRY IN THE ABSENCE OF THE HEMAGGLUTININ SIALIC ACID BINDING POCKET
Isabelle Szot, Emily Rumschlag-Booms.
Northeastern Illinois University, Chicago, IL.
H5N1 avian influenza virus, more commonly known as bird flu, is a highly pathogenic strain of influenza. Since 1997, there have been 650 individuals infected with bird flu with a mortality rate of over 60%. Though direct transmission to humans is possible, sustained human-to-human transmission has not been seen. However, a strengthened interaction between the viral protein, hemagglutinin (HA), and its hot cell receptor, sialic acid (SA), may lead to sustained transmission. This strengthened viral-host cell interaction is predicted to spark a pandemic. It has been proposed that a global pandemic could be sparked by influenza’s use of a co-receptor reinforcing viral attachment and entry. To further explore presence of this co-receptor, this study aimed to disrupt the traditional viral attachment mechanism between HA and SA. To disrupt the interaction of HA-SA, site-directed mutagenesis was used to create alanine substitutions at glycine135, serine136, and tyrosine98 in the sialic acid binding domain of HA. These amino acid residues were chosen due to their stability and to minimize conformational changes. If this interaction is blocked and viral entry is comparable to wild-type, this suggests that continued infection may be due to the presence of an additional co-receptor. Identification of the presence of a co-receptor can then be applied in development of novel therapeutic approaches for treating avian influenza.