Fusion activity of African henipavirus F proteins with a naturally occurring start codon directly upstream of the signal peptide.
Compared to the fusion proteins of pathogenic Nipah and Hendra viruses, the F protein of prototype African henipavirus GH-M74a displays a drastically reduced surface expression and fusion activity. A probable reason for limited F expression is the unusually long sequence located between the gene start and the signal peptide (SP) not present in other henipaviruses. Such a long pre-SP extension can prevent efficient ER translocation or protein maturation and processing. As its truncation can therefore enhance surface expression, the recent identification of a second in-frame start codon directly upstream of the SP in another African henipavirus F gene (GH-UP28) raised the question if such a naturally occurring minor sequence variation can lead to the synthesis of a pre-SP truncated translation product, thereby increasing the production of mature F proteins. To test this, we analyzed surface expression and biological activity of F genes carrying the second SP-proximal start codon of GH-UP28. Though we observed minor differences in the expression levels, introduction of the additional start codon did not result in an increased fusion activity, even if combined with further mutations in the pre-SP region. Thus, limited bioactivity of African henipavirus F protein is maintained even after sequence changes that alter the gene start allowing the production of F proteins without an unusually long pre-SP.
Institute of Virology, Philipps University Marburg, Marburg, Germany.
Michael
M
Weis
Institute of Virology, Philipps University Marburg, Marburg, Germany.
Laura
L
Behner
Institute of Virology, University of Bonn Medical Centre, Bonn, Germany.
Tabea
T
Binger
Institute of Virology, University of Bonn Medical Centre, Bonn, Germany.
Jan Felix
JF
Drexler
Institute of Virology, University of Bonn Medical Centre, Bonn, Germany.
Christian
C
Drosten
Institute of Virology, Philipps University Marburg, Marburg, Germany. Electronic address: maisner@staff.uni-marburg.de.
Andrea
A
Maisner
D000818:Animals; D002460:Cell Line; D018387:Codon, Initiator; D015870:Gene Expression; D045403:Henipavirus / Q000235:genetics / Q000502:physiology*; D021382:Protein Sorting Signals; D014760:Viral Fusion Proteins / Q000235:genetics / Q000378:metabolism*; D053586:Virus Internalization
D018387:Codon, Initiator; D021382:Protein Sorting Signals; D014760:Viral Fusion Proteins
African henipavirus; Fusion protein; Start codon; Surface expression