The small RING finger protein Z drives arenavirus budding: implications for antiviral strategies

Proceedings of the National Academy of Sciences of the United States of America
Mar PerezJuan C de la Torre

Abstract

By using a reverse genetics system that is based on the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV), we have identified the arenavirus small RING finger Z protein as the main driving force of virus budding. Both LCMV and Lassa fever virus (LFV) Z proteins exhibited self-budding activity, and both substituted efficiently for the late domain that is present in the Gag protein of Rous sarcoma virus. LCMV and LFV Z proteins contain proline-rich motifs that are characteristic of late domains. Mutations in the PPPY motif of LCMV Z severely impaired the formation of virus-like particles. LFV Z contains two different proline-rich motifs, PPPY and PTAP, which are separated by eight amino acids. Mutational analysis revealed that both motifs are required for efficient LFV Z-mediated budding. Both LCMV and LFV Z proteins recruited to the plasma membrane Tsg101, which is a component of the class E vacuolar protein sorting machinery that has been implicated in budding of HIV and Ebola virus. Targeting of Tsg101 by RNA interference caused a strong reduction in Z-mediated budding. These results indicate that Z is the arenavirus functional counterpart of the matrix proteins found in other negative strand enveloped RNA viruse...Continue Reading

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Citations

May 29, 2008·Archives of Virology·Shuiyun LanYuying Liang
Nov 26, 2010·Proceedings of the National Academy of Sciences of the United States of America·Andreas BergthalerDaniel D Pinschewer
Nov 23, 2011·Proceedings of the National Academy of Sciences of the United States of America·Philip J Kranzusch, Sean P J Whelan
Jun 30, 2010·International Immunology·Daniel D PinschewerAndreas Bergthaler
Jul 19, 2013·Journal of the Royal Society, Interface·David SchleyBenjamin W Neuman
Aug 27, 2010·Journal of Virology·Chao-Kuen LaiMichael M C Lai
Oct 29, 2010·Journal of Virology·Linda BrunotteStephan Günther
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Dec 19, 2008·Journal of Virology·Larissa KolesnikovaStephan Becker
Jan 15, 2010·Journal of Virology·Katrin SchlieWolfgang Garten
Jan 29, 2010·Journal of Virology·Allison GrosethStephan Becker
Oct 1, 2011·Journal of Virology·Maria Eugenia LoureiroNora Lopez
Feb 22, 2012·Journal of Virology·Shuzo UrataJuan Carlos de la Torre

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