University of Kentucky
The Effects of Hendra Virus Fusion Protein Charged Residues on Viral Fusion
Institution
University of Kentucky
Faculty Advisor/ Mentor
Rebecca Dutch
Abstract
The Hendra and Nipah viruses are two recently identified members of the Paramyxovirus family with no known vaccines yet. They can be transmitted from animals to humans (zoonotic) and have high fatality rates among humans, with a 1998 Nipah outbreak claiming over 100 lives. Therefore, it is of utmost importance that we learn more about them. I am working with Dr. Rebecca Dutch in the University of Kentucky's Department of Biochemistry. One focus of the Dutch lab is to study the specific proteins in these viruses that promote fusion between the viral membranes and the host cell membranes. In most viruses, these fusion (F) proteins have a positively charged plasmid DNA residue that interacts with the negatively charged membrane of the host cell. Interestingly, however, in Hendra and Nipah it is a negatively charged residue on the F protein that interacts with the negatively charged membrane of the host cell in the fusion process. Normally, the two charges would repel one another. My specific project involves altering the plasmid DNA residue to see if this has an effect on viral fusion. Using a sitedirected mutagenesis procedure, I changed the negatively charged amino acid residue, glutamic acid, to neutrally charged amino acid alanine. I am continuing my research to study the effects of this on the viral fusion process by transfecting the mutated plasmid DNA onto animal cells. The overall goals are to learn more about these new, potent viruses as well as to identify potential targets for antiviral drugs.
The Effects of Hendra Virus Fusion Protein Charged Residues on Viral Fusion
The Hendra and Nipah viruses are two recently identified members of the Paramyxovirus family with no known vaccines yet. They can be transmitted from animals to humans (zoonotic) and have high fatality rates among humans, with a 1998 Nipah outbreak claiming over 100 lives. Therefore, it is of utmost importance that we learn more about them. I am working with Dr. Rebecca Dutch in the University of Kentucky's Department of Biochemistry. One focus of the Dutch lab is to study the specific proteins in these viruses that promote fusion between the viral membranes and the host cell membranes. In most viruses, these fusion (F) proteins have a positively charged plasmid DNA residue that interacts with the negatively charged membrane of the host cell. Interestingly, however, in Hendra and Nipah it is a negatively charged residue on the F protein that interacts with the negatively charged membrane of the host cell in the fusion process. Normally, the two charges would repel one another. My specific project involves altering the plasmid DNA residue to see if this has an effect on viral fusion. Using a sitedirected mutagenesis procedure, I changed the negatively charged amino acid residue, glutamic acid, to neutrally charged amino acid alanine. I am continuing my research to study the effects of this on the viral fusion process by transfecting the mutated plasmid DNA onto animal cells. The overall goals are to learn more about these new, potent viruses as well as to identify potential targets for antiviral drugs.