Alix Serves As an Adaptor That Allows Human Parainfluenza Virus Type 1 to Interact with the Host Cell ESCRT System

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2013 Mar 26

PMID 23527201

Citations 10

Authors

Jim Boonyaratanakornkit

Henrick Schomacker

Peter Collins

Alexander Schmidt

Affiliations

Soon will be listed here.

Abstract

The cellular ESCRT (endosomal sorting complex required for transport) system functions in cargo-sorting, in the formation of intraluminal vesicles that comprise multivesicular bodies (MVB), and in cytokinesis, and this system can be hijacked by a number of enveloped viruses to promote budding. The respiratory pathogen human parainfluenza virus type I (HPIV1) encodes a nested set of accessory C proteins that play important roles in down-regulating viral transcription and replication, in suppressing the type I interferon (IFN) response, and in suppressing apoptosis. Deletion or mutation of the C proteins attenuates HPIV1 in vivo, and such mutants are being evaluated preclinically and clinically as vaccines. We show here that the C proteins interact and co-localize with the cellular protein Alix, which is a member of the class E vacuolar protein sorting (Vps) proteins that assemble at endosomal membranes into ESCRT complexes. The HPIV1 C proteins interact with the Bro1 domain of Alix at a site that is also required for the interaction between Alix and Chmp4b, a subunit of ESCRT-III. The C proteins are ubiquitinated and subjected to proteasome-mediated degradation, but the interaction with AlixBro1 protects the C proteins from degradation. Neither over-expression nor knock-down of Alix expression had an effect on HPIV1 replication, although this might be due to the large redundancy of Alix-like proteins. In contrast, knocking down the expression of Chmp4 led to an approximately 100-fold reduction in viral titer during infection with wild-type (WT) HPIV1. This level of reduction was similar to that observed for the viral mutant, P(C-) HPIV1, in which expression of the C proteins were knocked out. Chmp4 is capable of out-competing the HPIV1 C proteins for binding Alix. Together, this suggests a possible model in which Chmp4, through Alix, recruits the C proteins to a common site on intracellular membranes and facilitates budding.

Citing Articles

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Structural Insight into the Interaction of Sendai Virus C Protein with Alix To Stimulate Viral Budding.

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References

Itoh M, Isegawa Y, Hotta H, Homma M . Isolation of an avirulent mutant of Sendai virus with two amino acid mutations from a highly virulent field strain through adaptation to LLC-MK2 cells. J Gen Virol. 1997; 78 ( Pt 12):3207-15. DOI: 10.1099/0022-1317-78-12-3207. View

Chambers R, Takimoto T . Host specificity of the anti-interferon and anti-apoptosis activities of parainfluenza virus P/C gene products. J Gen Virol. 2009; 90(Pt 8):1906-1915. PMC: 2887575. DOI: 10.1099/vir.0.011700-0. View

Gosselin-Grenet A, Marq J, Abrami L, Garcin D, Roux L . Sendai virus budding in the course of an infection does not require Alix and VPS4A host factors. Virology. 2007; 365(1):101-12. DOI: 10.1016/j.virol.2007.03.039. View

Gottlieb J, Schulz T, Welte T, Fuehner T, Dierich M, Simon A . Community-acquired respiratory viral infections in lung transplant recipients: a single season cohort study. Transplantation. 2009; 87(10):1530-7. DOI: 10.1097/TP.0b013e3181a4857d. View

Lim K, Chew K, Tan J, Wang C, Chung K, Zhang Y . Parkin mediates nonclassical, proteasomal-independent ubiquitination of synphilin-1: implications for Lewy body formation. J Neurosci. 2005; 25(8):2002-9. PMC: 6726069. DOI: 10.1523/JNEUROSCI.4474-04.2005. View

Liu W, Duden R, Phair R, Lippincott-Schwartz J . ArfGAP1 dynamics and its role in COPI coat assembly on Golgi membranes of living cells. J Cell Biol. 2005; 168(7):1053-63. PMC: 2171832. DOI: 10.1083/jcb.200410142. View

Andrejeva J, Childs K, Young D, Carlos T, Stock N, Goodbourn S . The V proteins of paramyxoviruses bind the IFN-inducible RNA helicase, mda-5, and inhibit its activation of the IFN-beta promoter. Proc Natl Acad Sci U S A. 2004; 101(49):17264-9. PMC: 535396. DOI: 10.1073/pnas.0407639101. View

Murphy B, Prince G, Collins P, Van Wyke Coelingh K, Olmsted R, Spriggs M . Current approaches to the development of vaccines effective against parainfluenza and respiratory syncytial viruses. Virus Res. 1988; 11(1):1-15. DOI: 10.1016/0168-1702(88)90063-9. View

Kim J, Sitaraman S, Hierro A, Beach B, Odorizzi G, Hurley J . Structural basis for endosomal targeting by the Bro1 domain. Dev Cell. 2005; 8(6):937-47. PMC: 2862258. DOI: 10.1016/j.devcel.2005.04.001. View

10.

Presley J, Ward T, Pfeifer A, Siggia E, Phair R, Lippincott-Schwartz J . Dissection of COPI and Arf1 dynamics in vivo and role in Golgi membrane transport. Nature. 2002; 417(6885):187-93. DOI: 10.1038/417187a. View

11.

Irie T, Inoue M, Sakaguchi T . Significance of the YLDL motif in the M protein and Alix/AIP1 for Sendai virus budding in the context of virus infection. Virology. 2010; 405(2):334-41. DOI: 10.1016/j.virol.2010.06.031. View

12.

Pelchen-Matthews A, Kramer B, Marsh M . Infectious HIV-1 assembles in late endosomes in primary macrophages. J Cell Biol. 2003; 162(3):443-55. PMC: 2172706. DOI: 10.1083/jcb.200304008. View

13.

Hui D, Woo J, Hui E, Foo A, Ip M, To K . Influenza-like illness in residential care homes: a study of the incidence, aetiological agents, natural history and health resource utilisation. Thorax. 2008; 63(8):690-7. DOI: 10.1136/thx.2007.090951. View

14.

Luhtala N, Odorizzi G . Bro1 coordinates deubiquitination in the multivesicular body pathway by recruiting Doa4 to endosomes. J Cell Biol. 2004; 166(5):717-29. PMC: 2172414. DOI: 10.1083/jcb.200403139. View

15.

Bousse T, Chambers R, Scroggs R, Portner A, Takimoto T . Human parainfluenza virus type 1 but not Sendai virus replicates in human respiratory cells despite IFN treatment. Virus Res. 2006; 121(1):23-32. DOI: 10.1016/j.virusres.2006.03.012. View

16.

Huang F, Kirkpatrick D, Jiang X, Gygi S, Sorkin A . Differential regulation of EGF receptor internalization and degradation by multiubiquitination within the kinase domain. Mol Cell. 2006; 21(6):737-48. DOI: 10.1016/j.molcel.2006.02.018. View

17.

Irie T, Shimazu Y, Yoshida T, Sakaguchi T . The YLDL sequence within Sendai virus M protein is critical for budding of virus-like particles and interacts with Alix/AIP1 independently of C protein. J Virol. 2006; 81(5):2263-73. PMC: 1865917. DOI: 10.1128/JVI.02218-06. View

18.

Fisher R, Chung H, Zhai Q, Robinson H, Sundquist W, Hill C . Structural and biochemical studies of ALIX/AIP1 and its role in retrovirus budding. Cell. 2007; 128(5):841-52. DOI: 10.1016/j.cell.2007.01.035. View

19.

Sakaguchi T, Kato A, Sugahara F, Shimazu Y, Inoue M, Kiyotani K . AIP1/Alix is a binding partner of Sendai virus C protein and facilitates virus budding. J Virol. 2005; 79(14):8933-41. PMC: 1168738. DOI: 10.1128/JVI.79.14.8933-8941.2005. View

20.

Schomacker H, Hebner R, Boonyaratanakornkit J, Surman S, Amaro-Carambot E, Collins P . The C proteins of human parainfluenza virus type 1 block IFN signaling by binding and retaining Stat1 in perinuclear aggregates at the late endosome. PLoS One. 2012; 7(2):e28382. PMC: 3280236. DOI: 10.1371/journal.pone.0028382. View