Javier G. Magadán, Ph.D.

Title
Adjunct Professor
Institution
National University of Cuyo
Address
Casilla de Correo 56
City
Mendoza
Country
Argentina
Phone
+54 (261) 667-7547
E-mail
javimagadan[at]gmail.com
Research Field
Cell biology
Award Year
2007
Country Of Origin
Argentina
Mentor Name
Jonathan W. Yewdell, M.D., Ph.D.

Research

Influenza A virus (IAV) targets the ciliated epithelium of conducting airways through interaction of the viral envelope protein hemagglutinin (HA) with cell surface glycoproteins or glycolipids containing terminal sialic acid residues. Following IAV internalization by endocytosis, HA leads to fusion of the viral and cellular membranes by virtue of irreversible conformational changes into the HA molecule triggered by the mildly acidic pH within the virion-containing endosome, allowing the viral RNA genome to get inside the cytoplasm and thus instruct the cell to make new viral particles. The HA spike on the viral envelope is a homotrimeric type I integral membrane glycoprotein, where each of the mature monomers results from extensive post-translational modifications (i.e. trimming of N-linked carbohydrate chains, terminal glycosylation, sulfation, fatty acylation) during transport en route from the endoplasmic reticulum to the plasma membrane. Although current IAV vaccination programs in humans focus on inducing potent antibodies (Abs) that neutralize virus by binding to the highly immunogenic globular head domain of HA, little is known about how these Abs actually bind to their respective epitopes on mature trimerized HA. By screening and characterizing a number of monoclonal Abs directed to the Ca, Cb, Sa and Sb antigenic sites of HA, we attempt to get insight into the molecular basis by which maturation of HA (i.e., oligomerization and post-translational modifications) might affect HA antigenicity.