PMID- 18400865 OWN - NLM STAT- MEDLINE DCOM- 20080812 LR - 20211020 IS - 1098-5514 (Electronic) IS - 0022-538X (Print) IS - 0022-538X (Linking) VI - 82 IP - 12 DP - 2008 Jun TI - Site 1 protease is required for proteolytic processing of the glycoproteins of the South American hemorrhagic fever viruses Junin, Machupo, and Guanarito. PG - 6045-51 LID - 10.1128/JVI.02392-07 [doi] AB - The cellular proprotein convertase site 1 protease (S1P) has been implicated in the proteolytic processing of the glycoproteins (GPs) of Old World arenaviruses. Here we report that S1P is also involved in the processing of the GPs of the genetically more-distant South American hemorrhagic fever viruses Guanarito, Machupo, and Junin. Efficient cleavage of Guanarito virus GP, whose protease recognition sites deviate from the reported S1P consensus sequence, indicates a broader specificity of S1P than anticipated. Lack of GP processing of Junin virus dramatically reduced production of infectious virus and prevented cell-to-cell propagation. Infection of S1P-deficient cells resulted in viral persistence over several weeks without the emergence of escape variants able to use other cellular proteases for GP processing. FAU - Rojek, Jillian M AU - Rojek JM AD - Molecular and Integrative Neurosciences Department, The Scripps Research Institute, La Jolla, California 92037, USA. FAU - Lee, Andrew M AU - Lee AM FAU - Nguyen, NgocThao AU - Nguyen N FAU - Spiropoulou, Christina F AU - Spiropoulou CF FAU - Kunz, Stefan AU - Kunz S LA - eng GR - R21 AI065560/AI/NIAID NIH HHS/United States GR - U54 AI065359/AI/NIAID NIH HHS/United States GR - 1U54 AI065359/AI/NIAID NIH HHS/United States GR - AI065560/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20080409 PL - United States TA - J Virol JT - Journal of virology JID - 0113724 RN - 0 (Glycoproteins) RN - 0 (Protein Precursors) RN - 0 (Recombinant Proteins) RN - 147336-22-9 (Green Fluorescent Proteins) RN - EC 1.13.12.- (Luciferases) RN - EC 3.4.21.- (Proprotein Convertases) RN - EC 3.4.21.- (Serine Endopeptidases) RN - EC 3.4.21.112 (membrane-bound transcription factor peptidase, site 1) SB - IM MH - Amino Acid Sequence MH - Animals MH - Arenaviruses, New World/*metabolism MH - CHO Cells MH - Cell Line MH - Chlorocebus aethiops MH - Cricetinae MH - Cricetulus MH - Glycoproteins/*metabolism MH - Green Fluorescent Proteins/metabolism MH - Humans MH - Kidney/cytology MH - Luciferases/analysis/metabolism MH - Molecular Sequence Data MH - Mutation MH - Proprotein Convertases/chemistry/genetics/*metabolism MH - Protein Precursors/chemistry/metabolism MH - *Protein Processing, Post-Translational MH - Recombinant Proteins/chemistry/metabolism MH - Serine Endopeptidases/chemistry/genetics/*metabolism MH - Transfection MH - Vero Cells PMC - PMC2395157 EDAT- 2008/04/11 09:00 MHDA- 2008/08/13 09:00 PMCR- 2008/10/01 CRDT- 2008/04/11 09:00 PHST- 2008/04/11 09:00 [pubmed] PHST- 2008/08/13 09:00 [medline] PHST- 2008/04/11 09:00 [entrez] PHST- 2008/10/01 00:00 [pmc-release] AID - JVI.02392-07 [pii] AID - 2392-07 [pii] AID - 10.1128/JVI.02392-07 [doi] PST - ppublish SO - J Virol. 2008 Jun;82(12):6045-51. doi: 10.1128/JVI.02392-07. Epub 2008 Apr 9.