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The Molecular Tool‐Kit of Viral Hemorrhagic Fevers
Author(s) -
Ollmann Saphire Erica,
Bornholdt Zach,
Fusco Marnie,
Abelson Dafna,
Hashiguchi Takao,
Lee Jeffrey,
Kawaoka Yoshihiro,
Dye John,
Crowe James
Publication year - 2015
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.29.1_supplement.102.1
Subject(s) - vp40 , ebolavirus , microbiology and biotechnology , viral life cycle , random hexamer , viral protein , biology , virus , endosome , epitope , virology , tsg101 , viral matrix protein , ebola virus , gene , antibody , viral replication , genetics , microrna , microvesicles , intracellular
Ebola and Marburg viruses cause hemorrhagic fever with up to 90% lethality, and their genomes encode just seven genes. The few gene products encoded, their “tool‐kit”, are leveraged into a greater array of functions, by remodeling or rearranging of the 3D protein structures. The surface glycoprotein adopts a massive, heavily glycosylated form on the viral surface, but is remodeled into a minimal receptor‐binding core once inside the endosome. As a result, binding of many potential antibodies is lost as their epitopes are stripped form the virus. Crystal structures of potently neutralizing antibodies, however, reveal how one remains bound and reaches into the cryptic receptor‐binding site. Others likely neutralize by locking the GP structure in place. Additional protein transformation takes place at the other end of the virus life cycle, assembly and budding of nascent virions. Through multiple crystal structures, biochemistry and cellular microscopy, we illustrated that the matrix protein VP40 rearranges into different structures, each with a distinct function required for the ebolavirus life cycle. A butterfly‐shaped VP40 dimer trafficks to the cellular membrane. A distinct, linear hexamer structure is critical for assembly and release of the virion. A third structure of VP40, an RNA‐binding ring, regulates viral transcription inside infected cells.