Involvement of p32 and microtubules in alteration of mitochondrial functions by rubella virus.
The interaction of the rubella virus (RV) capsid (C) protein and the mitochondrial p32 protein is believed to participate in virus replication. In this study, the physiological significance of the association of RV with mitochondria was investigated by silencing p32 through RNA interference. It was demonstrated that downregulation of p32 interferes with microtubule-directed redistribution of mitochondria in RV-infected cells. However, the association of the viral C protein with mitochondria was not affected. When cell lines either pretreated with respiratory chain inhibitors or cultivated under (mild) hypoxic conditions were infected with RV, viral replication was reduced in a time-dependent fashion. Additionally, RV infection induces increased activity of mitochondrial electron transport chain complex III, which was associated with an increase in the mitochondrial membrane potential. These effects are outstanding among the examples of mitochondrial alterations caused by viruses. In contrast to the preferential localization of p32 to the mitochondrial matrix in most cell lines, RV-permissive cell lines were characterized by an almost exclusive membrane association of p32. Conceivably, this contributes to p32 function(s) during RV replication. The data presented suggest that p32 fulfills an essential function for RV replication in directing trafficking of mitochondria near sites of viral replication to meet the energy demands of the virus.
Institute of Virology, University of Leipzig, Johannisallee 30, Leipzig D-04103, Germany.
C
C
Claus
S
S
Chey
S
S
Heinrich
M
M
Reins
B
B
Richardt
S
S
Pinkert
H
H
Fechner
F
F
Gaunitz
I
I
Schäfer
P
P
Seibel
U G
UG
Liebert
D000818:Animals; D002352:Carrier Proteins; D002460:Cell Line; D004579:Electron Transport; D020868:Gene Silencing; D054884:Host-Pathogen Interactions; D006801:Humans; D053078:Membrane Potential, Mitochondrial; D008870:Microtubules / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism* / Q000821:virology*; D024101:Mitochondrial Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D034622:RNA Interference; D012412:Rubella virus / Q000472:pathogenicity*; D014758:Viral Core Proteins / Q000378:metabolism*
C087299:C1QBP protein, human; D002352:Carrier Proteins; D024101:Mitochondrial Proteins; D014758:Viral Core Proteins; C074573:nucleocapsid protein (C), rubella virus
Cell Cycle. 2007 Jan 1;6(1):36-8
17245115
Virology. 2010 Sep 30;405(2):579-91
20655079
Cancer Res. 2008 Sep 1;68(17):7210-8
18757437
Virus Res. 2002 May 10;85(2):151-61
12034482
J Biol Chem. 2002 Feb 15;277(7):5247-55
11698413
Nature. 2005 May 26;435(7041):502-6
15917810
Arch Virol. 1976;52(1-2):19-27
999519
J Gen Virol. 2006 Oct;87(Pt 10):3029-3037
16963762
J Biol Chem. 2008 Jul 11;283(28):19636-45
18460468
Virology. 2010 Oct 25;406(2):212-27
20696450
Biochem Biophys Res Commun. 2000 May 19;271(3):610-4
10814509
Cancer Cell. 2008 Jun;13(6):542-53
18538737
J Virol. 1998 Sep;72(9):7583-8
9696857
J Gen Virol. 1979 Aug;44(2):323-31
230286
Int J Biochem Cell Biol. 2010 May;42(5):604-22
19931409
Genome Biol. 2002 Jun 18;3(7):RESEARCH0034
12184808
Oncogene. 2007 Oct 11;26(46):6677-83
17486078
Microbiol Immunol. 2004;48(11):823-9
15557740
Apoptosis. 2006 May;11(5):861-74
16544101
Cell Motil Cytoskeleton. 1998;40(4):368-78
9712266
J Cell Biochem. 2010 May;110(1):118-28
20217898
Semin Cell Dev Biol. 2009 May;20(3):346-53
19530278
J Biol Chem. 1997 Sep 26;272(39):24363-70
9305894
Biol Chem. 2009 Sep;390(9):915-9
19453272
Gene Ther. 2007 Jun;14(12):960-71
17377597
J Virol. 2006 Apr;80(8):3966-74
16571813
Ann N Y Acad Sci. 2004 Apr;1011:123-32
15126290
J Biomed Sci. 2009 Sep 02;16:80
19725950
J Immunol Methods. 2007 Jan 10;318(1-2):11-9
17141265
J Virol. 2007 Feb;81(4):1714-26
17151129
Nucleic Acids Res. 2008 Apr;36(7):e44
18353857
Yeast. 2006 Mar;23(4):279-91
16544270
Virology. 1994 Apr;200(1):307-12
8128633
J Neurosci. 2010 Jun 30;30(26):8984-92
20592219
Cell Microbiol. 2007 Apr;9(4):875-90
17087733
Teratology. 1998 Jul;58(1):13-23
9699240
J Virol. 2005 Aug;79(16):10807-20
16051872
Clin Chim Acta. 2008 Sep;395(1-2):38-41
18502205
J Virol. 2000 Jun;74(12):5569-76
10823864
J Gen Virol. 1998 Jul;79 ( Pt 7):1677-85
9680131
Apoptosis. 2010 Jan;15(1):28-40
19771519
Mol Cell Biol. 2010 Mar;30(6):1303-18
20100866
J Pineal Res. 2000 May;28(4):242-8
10831160
J Virol. 2010 Jan;84(1):119-30
19846524
Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):3572-7
10097078