The nipah virus fusion protein is cleaved within the endosomal compartment.
Nipah virus (NiV) is a recently emerged and highly pathogenic paramyxovirus that causes a systemic infection in animals and humans and can infect a wide range of cultured cells. Interestingly, the NiV fusion (F) protein has a single arginine at the cleavage site similar to paramyxoviruses that are activated by exogenous trypsin-like enzymes only present in specific cells and tissues and therefore only cause localized infections. We show here that NiV F activation is not mediated by an exogenous serum protease but by an endogenous ubiquitous cellular protease after endocytosis of the protein. In addition to endocytosis, acidification of the endosome is a prerequisite for F cleavage. These results show that activation of the NiV F protein depends on a type of proteolytic cleavage that is clearly different from what is known for other paramyxoviral and orthomyxoviral fusion proteins. To our knowledge, this is the first example of a viral class I fusion protein whose activation depends on clathrin-mediated constitutive endocytosis.
Diederich
Sandra
S
Institute of Virology, Philipps University of Marburg, Germany.
Moll
Markus
M
Klenk
Hans-Dieter
HD
Maisner
Andrea
A
D000595:Amino Acid Sequence; D000818:Animals; D002522:Chlorocebus aethiops; D004285:Dogs; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008969:Molecular Sequence Data; D045405:Nipah Virus / Q000737:chemistry*; D014709:Vero Cells; D014760:Viral Fusion Proteins / Q000378:metabolism
D014760:Viral Fusion Proteins