Premium
Targeting the Hendra Virus Fusion Protein Transmembrane Domain to Inhibit Viral Fusion
Author(s) -
Barrett Chelsea,
Webb Stacy,
Dutch Rebecca
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.603.19
Subject(s) - hendra virus , heptad repeat , transmembrane protein , lipid bilayer fusion , transmembrane domain , fusion protein , viral entry , biology , virus , virology , viral envelope , paramyxoviridae , glycoprotein , microbiology and biotechnology , peptide sequence , biochemistry , viral replication , ebola virus , receptor , viral disease , gene , recombinant dna
Hendra Virus is a zoonotic virus in the family Paramyxoviridae. It is an enveloped, negative sense single stranded RNA virus that is highly pathogenic, but currently there is no approved antiviral therapeutic or vaccine. Further elucidation of the mechanisms that underlie viral entry into a cell will assist in presenting additional targets for therapeutics. Two surface glycoproteins, the attachment protein (G) and the fusion protein (F), are critical for viral binding and fusion. When a proper signal is received by the Hendra F protein, it undergoes a large, essentially irreversible, conformational change resulting in the fusion of the virus and target cell membranes. Previous research has demonstrated that the Hendra F protein associates as a homo‐trimer, and that the transmembrane domain (TMD), plays a key role in this association, as well as overall protein stability. To further characterize this role of the TMD in the fusion process, exogenous Hendra TM constructs were created containing the cytoplasmic tail, a signal peptide, an HA tag and varying lengths of the heptad repeat B region. When these TM constructs were co‐expressed with the full length Hendra F protein, a significant reduction in the expression and stability of the full length protein was observed. In contrast, when the Hendra TM constructs were co‐expressed with Parainfluenza Virus 5 (PIV5) F protein, another member of Paramyxoviridae, no decrease in F protein expression was observed, suggesting the interactions between transmembrane domains are sequence specific. Further experimentation is ongoing to further characterize the TMD interactions, however specifically targeting the TMD of F proteins may present a unique therapeutic target. Support or Funding Information University of Kentucky, Department of Molecular and Cellular Biochemistry