RING finger Z protein of lymphocytic choriomeningitis virus (LCMV) inhibits transcription and RNA replication of an LCMV S-segment minigenome.
Arenaviruses have a bisegmented negative-strand RNA genome whose proteomic capability is limited to only four polypeptides, namely, nucleoprotein (NP), surface glycoprotein (GP) that is proteolytically processed into GP1+GP2, polymerase (L), and a small (11-kDa) RING finger protein (Z). The role of Z during the Lymphocytic choriomeningitis virus (LCMV) life cycle is poorly understood. We investigated the function of Z in virus transcription and replication by using a reverse genetic system for the prototypic arenavirus LCMV. This system involves an LCMV minigenome and the minimal viral trans-acting factors (NP and L), expressed from separated cotransfected plasmids. Cotransfection of the Z cDNA strongly inhibited LCMV minigenome expression. The effect required synthesis of Z protein; its magnitude was dose dependent and occurred with levels of Z protein substantially lower than those observed in LCMV-infected cells. Coexpression of Z did not prevent the encapsidation of plasmid supplied minigenome, but it affected both transcription and RNA replication similarly. Mutations in Z that unfolded its RING finger domain eliminated its inhibitory activity, but RING proteins not related to Z did not affect LCMV minigenome expression. Consistent with the minigenome results, cells transiently expressing Z exhibited decreased susceptibility to infection with LCMV.
Cornu
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TI
Division of Virology, Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California 92037, USA.
de la Torre
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JC
D000818:Animals; D002352:Carrier Proteins / Q000502:physiology*; D002460:Cell Line; D006224:Cricetinae; D016679:Genome, Viral; D047908:Intracellular Signaling Peptides and Proteins; D008217:Lymphocytic choriomeningitis virus / Q000502:physiology*; D009154:Mutation; D012367:RNA, Viral / Q000502:physiology; D014779:Virus Replication
D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D012367:RNA, Viral; C117526:p11 Z protein, Lymphocytic choriomeningitis virus