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.
Division of Virology, Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California 92037, USA.
Tatjana I
TI
Cornu
Heinz
H
Feldmann
Juan Carlos
JC
de la Torre
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