Ubiquitous activation of the Nipah virus fusion protein does not require a basic amino acid at the cleavage site.
Nipah virus (NiV), a highly pathogenic paramyxovirus, causes a systemic infection in vivo and is able to replicate in cultured cells of many species and organs. Such pantropic paramyxoviruses generally encode fusion (F) proteins with multibasic cleavage sites activated by furin or other ubiquitous intracellular host cell proteases. In contrast, NiV has an F protein with a single arginine (R109) at the cleavage site, as is the case with paramyxoviruses that are activated by trypsin-like proteases only present in specific cells or tissues and therefore only cause localized infections. Unlike these viruses, cleavage of the NiV F protein is ubiquitous and does not require the addition of exogenous proteases in cell culture. To determine the importance of the amino acid sequence at the NiV F protein cleavage site for ubiquitous activation, we generated NiV F proteins with mutations around R109. Surprisingly, neither the exchange of amino acids upstream of R109 nor replacement of the basic residue itself interfered with F cleavage. Thus, R109 is not essential for F cleavage and activation. Our data demonstrate that NiV F-protein activation depends on a novel type of proteolytic cleavage that has not yet been described for any other paramyxovirus F protein. NiV F activation is mediated by a ubiquitous protease that requires neither a monobasic nor a multibasic cleavage site and therefore differs from the furin- or trypsin-like proteases known to activate other ortho- and paramyxovirus fusion proteins.
Institut für Virologie, Robert-Koch-Str. 17, 35037 Marburg, Germany.
Markus
M
Moll
Sandra
S
Diederich
Hans-Dieter
HD
Klenk
Markus
M
Czub
Andrea
A
Maisner
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D024361:Amino Acids, Basic / Q000737:chemistry; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D002460:Cell Line; D004285:Dogs; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D045405:Nipah Virus / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D010252:Paramyxoviridae / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D014760:Viral Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*
D024361:Amino Acids, Basic; D014760:Viral Fusion Proteins