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Defining the Role of the L/I Zipper in the Stability of Paramyxo‐ and Pneumovirus F Proteins
Author(s) -
Branttie Jean Mawuena,
Webb Stacy R.,
Dutch Rebecca E.
Publication year - 2018
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.2018.32.1_supplement.526.9
Subject(s) - leucine zipper , zipper , heptad repeat , virus , biology , virology , lipid bilayer fusion , mutant , cell fusion , glycoprotein , viral envelope , rna virus , microbiology and biotechnology , viral entry , rna , cell , genetics , peptide sequence , gene , viral replication , algorithm , computer science
Paramyxoviruses such as Hendra virus (HeV) and Measles virus (MeV) are important pathogens of worldwide significance. Others such as Parainfluenza virus (PIV5) are widely used as paramyxovirus model systems. Despite their prevalence, currently, no FDA‐approved vaccines or antiviral therapeutics are available against them. Paramyxoviruses consist of a single‐stranded negative sense RNA genome enveloped in a host‐derive membrane. Paramyxovirus glycoproteins play an important role in infectivity: the attachment protein (G, HN, or H) docks the viral particle to the host cell, and the fusion protein, (F), drives fusion with a host cell membrane, which allows the release of viral contents into the host cell. To promote successful fusion, the F protein undergoes dramatic, essentially irreversible conformational changes which must be carefully timed. To avoid unproductive triggering events, F is held in a metastable prefusion conformation until the right signal for fusion occurs. Previous studies in HeV F have shown that the transmembrane (TM) domain is important for prefusion stability with a leucine/isoleucine (L/I) zipper playing a key role. Furthermore, similar L/I zipper motifs are present across the paramyxovirus and the closely related pneumovirus families. To define the significance of the L/I zipper motifs in other paramyxo‐ and pneumovirus F proteins, we created a PIV5 F mutant protein which has alanine substitutions to the L/I zipper in the TM domain. Our preliminary data suggest that the mutant expresses; however, compared to wild type, which demonstrates a strong localization to the plasma membrane, the mutant shows a ubiquitous distribution in cells. This suggests that the mutant undergoes different trafficking events compared to the wild type. Further studies will be performed to quantify surface and total expression of the mutant, and also examine its stability and fusogenic activity. The effect of the L/I zipper will also be investigated in the context of Human metapneumovirus, a pneumovirus in order to determine whether the TM domain of paramyxo‐ and pneumoviruses present a broad therapeutic target. Support or Funding Information We gratefully acknowledge the NIH/NIAID for supporting our research grant R01 AI051517 This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .