Cells expressing the RING finger Z protein are resistant to arenavirus infection.
Arenaviruses include Lassa fever virus (LFV) and the South American hemorrhagic fever viruses. These viruses cause severe human disease, and they pose a threat as agents of bioterrorism. Arenaviruses are enveloped viruses with a bisegmented negative-strand RNA genome whose proteomic capability is limited to four polypeptides: nucleoprotein (NP); surface glycoprotein (GP), which is proteolytically processed into GP1 and GP2; polymerase (L); and a small (11-kDa) RING finger protein (Z). Our investigators have previously shown that Z has a strong inhibitory activity on RNA synthesis mediated by the polymerase of the prototypic arenavirus, lymphocytic choriomeningitis virus (LCMV). In this report we show that cells transduced with a replication-deficient recombinant adenovirus expressing Z (rAd-Z) are resistant to LCMV and LFV infection. Virus cell entry mediated by LCMV or LFV GP was not affected in rAd-Z-transduced cells, but both virus transcription and replication were strongly and specifically inhibited, which resulted in a dramatic reduction in production of infectious virus. These findings open new avenues for developing antiviral strategies to combat the highly pathogenic human arenaviruses, including LFV.
Cornu
Tatjana I
TI
Division of Virology, Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California 92037, USA.
Feldmann
Heinz
H
de la Torre
Juan Carlos
JC
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001117:Arenaviridae Infections / Q000821:virology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*; D002522:Chlorocebus aethiops; D050556:Fatty Acid-Binding Proteins; D006801:Humans; D007836:Lassa virus / Q000187:drug effects / Q000378:metabolism / Q000472:pathogenicity*; D008217:Lymphocytic choriomeningitis virus / Q000187:drug effects / Q000378:metabolism / Q000472:pathogenicity*; D014158:Transcription, Genetic / Q000187:drug effects; D014161:Transduction, Genetic; D014709:Vero Cells; D014779:Virus Replication / Q000187:drug effects
D002352:Carrier Proteins; D050556:Fatty Acid-Binding Proteins