The Lymphocytic Choriomeningitis Virus Matrix Protein PPXY Late Domain Drives the Production of Defective Interfering Particles

Overview

Journal PLoS Pathog

Specialty Microbiology

Date 2016 Mar 25

PMID 27010636

Citations 23

Authors

Christopher M Ziegler

Philip Eisenhauer

Emily A Bruce

Marion E Weir

Benjamin R King

Joseph P Klaus

Dimitry N Krementsov

David J Shirley

Bryan A Ballif

Jason Botten

Affiliations

Soon will be listed here.

Abstract

Arenaviruses cause severe diseases in humans but establish asymptomatic, lifelong infections in rodent reservoirs. Persistently-infected rodents harbor high levels of defective interfering (DI) particles, which are thought to be important for establishing persistence and mitigating virus-induced cytopathic effect. Little is known about what drives the production of DI particles. We show that neither the PPXY late domain encoded within the lymphocytic choriomeningitis virus (LCMV) matrix protein nor a functional endosomal sorting complex transport (ESCRT) pathway is absolutely required for the generation of standard infectious virus particles. In contrast, DI particle release critically requires the PPXY late domain and is ESCRT-dependent. Additionally, the terminal tyrosine in the PPXY motif is reversibly phosphorylated and our findings indicate that this posttranslational modification may regulate DI particle formation. Thus we have uncovered a new role for the PPXY late domain and a possible mechanism for its regulation.

Citing Articles

Seoul orthohantavirus evades innate immune activation by reservoir endothelial cells.

Klimaj S, LaPointe A, Martinez K, Acosta E, Kell A PLoS Pathog. 2024; 20(11):e1012728.

PMID: 39585900 PMC: 11627401. DOI: 10.1371/journal.ppat.1012728.

Defective viral genomes: advances in understanding their generation, function, and impact on infection outcomes.

Brennan J, Sun Y mBio. 2024; 15(5):e0069224.

PMID: 38567955 PMC: 11077978. DOI: 10.1128/mbio.00692-24.

S RNA Intergenic Deletions Drive Viral Interference during Arenavirus Infections.

Hackbart M, Lopez C bioRxiv. 2023; .

PMID: 37961573 PMC: 10635013. DOI: 10.1101/2023.10.31.564889.

Persistent Reptarenavirus and Hartmanivirus Infection in Cultured Boid Cells.

Lintala A, Szirovicza L, Kipar A, Hetzel U, Hepojoki J Microbiol Spectr. 2022; 10(4):e0158522.

PMID: 35862992 PMC: 9430581. DOI: 10.1128/spectrum.01585-22.

Masitinib is a broad coronavirus 3CL inhibitor that blocks replication of SARS-CoV-2.

Drayman N, DeMarco J, Jones K, Azizi S, Froggatt H, Tan K Science. 2021; 373(6557):931-936.

PMID: 34285133 PMC: 8809056. DOI: 10.1126/science.abg5827.

References

Garcia M, Reynolds T, Mothes W, Robek M . Functional characterization of the putative hepatitis B virus core protein late domain using retrovirus chimeras. PLoS One. 2013; 8(8):e72845. PMC: 3756966. DOI: 10.1371/journal.pone.0072845. View

Votteler J, Sundquist W . Virus budding and the ESCRT pathway. Cell Host Microbe. 2013; 14(3):232-41. PMC: 3819203. DOI: 10.1016/j.chom.2013.08.012. View

Klaus J, Eisenhauer P, Russo J, Mason A, Do D, King B . The intracellular cargo receptor ERGIC-53 is required for the production of infectious arenavirus, coronavirus, and filovirus particles. Cell Host Microbe. 2013; 14(5):522-34. PMC: 3999090. DOI: 10.1016/j.chom.2013.10.010. View

Degasperi A, Birtwistle M, Volinsky N, Rauch J, Kolch W, Kholodenko B . Evaluating strategies to normalise biological replicates of Western blot data. PLoS One. 2014; 9(1):e87293. PMC: 3903630. DOI: 10.1371/journal.pone.0087293. View

Strecker T, Eichler R, Ter Meulen J, Weissenhorn W, Klenk H, Garten W . Lassa virus Z protein is a matrix protein and sufficient for the release of virus-like particles [corrected]. J Virol. 2003; 77(19):10700-5. PMC: 228511. DOI: 10.1128/jvi.77.19.10700-10705.2003. View

Perez M, Craven R, de la Torre J . The small RING finger protein Z drives arenavirus budding: implications for antiviral strategies. Proc Natl Acad Sci U S A. 2003; 100(22):12978-83. PMC: 240730. DOI: 10.1073/pnas.2133782100. View

Stojdl D, Lichty B, tenOever B, Paterson J, Power A, Knowles S . VSV strains with defects in their ability to shutdown innate immunity are potent systemic anti-cancer agents. Cancer Cell. 2003; 4(4):263-75. DOI: 10.1016/s1535-6108(03)00241-1. View

Dalal S, Rosser M, Cyr D, Hanson P . Distinct roles for the AAA ATPases NSF and p97 in the secretory pathway. Mol Biol Cell. 2003; 15(2):637-48. PMC: 329284. DOI: 10.1091/mbc.e03-02-0097. View

Cornu T, Feldmann H, de la Torre J . Cells expressing the RING finger Z protein are resistant to arenavirus infection. J Virol. 2004; 78(6):2979-83. PMC: 353761. DOI: 10.1128/jvi.78.6.2979-2983.2004. View

10.

Hemonnot B, Cartier C, Gay B, Rebuffat S, Bardy M, Devaux C . The host cell MAP kinase ERK-2 regulates viral assembly and release by phosphorylating the p6gag protein of HIV-1. J Biol Chem. 2004; 279(31):32426-34. DOI: 10.1074/jbc.M313137200. View

11.

Perez M, Greenwald D, de la Torre J . Myristoylation of the RING finger Z protein is essential for arenavirus budding. J Virol. 2004; 78(20):11443-8. PMC: 521847. DOI: 10.1128/JVI.78.20.11443-11448.2004. View

12.

Huang A, Baltimore D . Defective viral particles and viral disease processes. Nature. 1970; 226(5243):325-7. DOI: 10.1038/226325a0. View

13.

Welsh R, Pfau C . Determinants of lymphocytic choriomeningitis interference. J Gen Virol. 1972; 14(2):177-87. DOI: 10.1099/0022-1317-14-2-177. View

14.

Staneck L, Trowbridge R, Welsh R, Wright E, Pfau C . Arenaviruses: cellular response to long-term in vitro infection with parana and lymphocytic choriomeningitis viruses. Infect Immun. 1972; 6(4):444-50. PMC: 422557. DOI: 10.1128/iai.6.4.444-450.1972. View

15.

Welsh R, OConnell C, Pfau C . Properties of defective lymphocytic choriomeningitis virus. J Gen Virol. 1972; 17(3):355-9. DOI: 10.1099/0022-1317-17-3-355. View

16.

Huang A . Defective interfering viruses. Annu Rev Microbiol. 1973; 27:101-17. DOI: 10.1146/annurev.mi.27.100173.000533. View

17.

Popescu M, Schaefer H, Lehmann-Grube F . Homologous interference of lymphocytic choriomeningitis virus: detection and measurement of interference focus-forming units. J Virol. 1976; 20(1):1-8. PMC: 354958. DOI: 10.1128/JVI.20.1.1-8.1976. View

18.

Popescu M, Lehmann-Grube F . Defective interfering particles in mice infected with lymphocytic choriomeningitis virus. Virology. 1977; 77(1):78-83. DOI: 10.1016/0042-6822(77)90407-x. View

19.

Dutko F, Pfau C . Arenavirus defective interfering particles mask the cell-killing potential of standard virus. J Gen Virol. 1978; 38(2):195-208. DOI: 10.1099/0022-1317-38-2-195. View

20.

Welsh Jr R, Buchmeier M . Protein analysis of defective interfering lymphocytic choriomeningitis virus and persistently infected cells. Virology. 1979; 96(2):503-15. DOI: 10.1016/0042-6822(79)90107-7. View