Cleavage of the Junin virus nucleoprotein serves a decoy function to inhibit the induction of apoptosis during infection.
The regulation of apoptosis during infection is an important factor for host survival and, in some cases, also for the virus life cycle. At the same time, mechanisms to prevent the induction of apoptosis have been observed in numerous viral pathogens, but until now the role of apoptosis during arenavirus infection has not been investigated. Junin virus (JUNV) belongs to the New World arenavirus serogroup of the Arenaviridae and is the causative agent of Argentine hemorrhagic fever. We have demonstrated that infection with JUNV in cell culture does not induce apoptosis but leads to cleavage of the nucleoprotein (NP) into discrete products resembling caspase cleavage events. Similar specific NP degradation patterns were also observed in NP-transfected cell lines, and a closer examination of the sequence of NP showed several putative caspase cleavage motifs. Point mutations that abolished these cleavage motifs were consistent with the loss of certain cleavage products. Consistent with these data, further studies showed that treatment with a caspase inhibitor also reduced NP cleavage, indicating that the observed cleavage events were occurring as a result of caspase activity with NP as a substrate. Finally, we showed that expression of NP suppresses the cleavage of caspase 3 in cells treated with an apoptosis activator. Based on these findings, we propose that NP functions as a decoy substrate for caspase cleavage in order to inhibit the induction of apoptosis in JUNV-infected cells.
Institut für Virologie, Philipps Universität Marburg, Marburg, Germany.
Svenja
S
Wolff
Stephan
S
Becker
Allison
A
Groseth
D000818:Animals; D017209:Apoptosis; D020169:Caspases / Q000378:metabolism*; D002522:Chlorocebus aethiops; D057131:Immune Evasion; D018051:Junin virus / Q000472:pathogenicity*; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D009698:Nucleoproteins / Q000235:genetics / Q000378:metabolism*; D017354:Point Mutation; D014709:Vero Cells
D050505:Mutant Proteins; D009698:Nucleoproteins; D020169:Caspases