Accession Number:

ADA421315

Title:

Structural and Functional Studies on the Fusion and Attachment Envelope Glycoproteins of Nipah Virus and Hendra Virus

Descriptive Note:

Doctoral thesis

Corporate Author:

UNIFORMED SERVICES UNIV OF THE HEALTH SCIENCES BETHESDA MD

Personal Author(s):

Report Date:

2003-01-01

Pagination or Media Count:

193.0

Abstract:

Nipah virus NiV and Hendra HeV virus are emerging, biosafety level 4 paramyxoviruses responsible for fatal zoonotic infections of humans from pigs and horses, respectively, and are the prototypic members of a new Paramyxovirinae genus called Henipavirus. These enveloped, negative-sense RNA viruses infect cells through a pH-independent membrane fusion event mediated through the actions of their attachment G and fusion F envelope glycoproteins, which are also the principal antigens to which neutralizing antibodies are directed. Understanding the biological and functional features of the viral glycoproteins will help define the characteristics and properties of these novel viruses, and may provide insights into membrane fusion mechanisms, the virus infection process, and towards the development of therapeutics. Here, recombinant vaccinia virus vectors were generated to express the NiV and HeV glycoproteins. Glycoprotein functions and their cellular tropism characteristics were examined with a quantitative assay for membrane fusion. NiV and HeV glycoprotein-mediated fusion could be blocked by virus-specific antisera or synthetic peptides corresponding to the C-terminal alpha-helical heptad repeats of NiV or HeV F. Both F and G glycoproteins were required for membrane fusion and a broad species and cellular tropism pattern was observed for both HeV and NiV. Further, protease treatment of receptive host cells abolished viral glycoprotein-mediated fusion activity, suggesting a cell-surface protein serves as a receptor for these viruses. In addition, interactions between the glycoproteins of the paramyxoviruses have not been well defined, but studies reported here show the NiV and HeV glycoproteins are capable of a highly efficient heterotypic functional activity amongst themselves, but not with other related paramyxoviruses.

Subject Categories:

  • Biochemistry
  • Microbiology

Distribution Statement:

APPROVED FOR PUBLIC RELEASE