Herpes simplex virus type 1 production requires a functional ESCRT-III complex but is independent of TSG101 and ALIX expression.
Herpes simplex virus type 1 (HSV-1) acquires its mature virus envelope by budding into the lumen of cytoplasmic membranous compartments carrying the viral glycoproteins. In a cellular context, a budding process with identical topology occurs during the formation of intraluminal vesicles in multivesicular bodies. The cellular machinery that mediates this budding process is composed of four protein complexes termed endosomal sorting complexes required for transport (ESCRTs) and several associated proteins, including the ATPase VPS4. We have recently shown that functional VPS4 is specifically required for the cytoplasmic envelopment of HSV-1. We now demonstrate that, consistent with a role of VPS4 in virus envelopment, dominant-negative ESCRT-III proteins potently block HSV-1 production. Retroviruses are known to recruit the ESCRT machinery by small peptide motifs termed late domains. These late domains interact with various ESCRT components and thereby promote ESCRT recruitment. The best-characterized late-domain interacting ESCRT proteins are ALIX and TSG101. The presence of potential ALIX and TSG101 binding sequence motifs in various structural HSV-1 proteins suggested a functional role of these proteins in HSV-1 envelopment. We therefore used a set of dominant-negative proteins, as well as RNA interference, to characterize the contribution of ALIX and TSG101 to HSV-1 production. Interestingly, despite the strict requirement for a functional ESCRT-III complex, our data suggest that HSV-1 production is independent of ALIX and TSG101 expression. In line with these data, we also find that ESCRT-III proteins and VPS4A/B are specifically incorporated into mature HSV-1 virions.
Pawliczek
Tobias
T
Division of Virology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, United Kingdom.
Crump
Colin M
CM
D000818:Animals; D001692:Biological Transport / Q000502:physiology; D019556:COS Cells; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002522:Chlorocebus aethiops; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D056827:Endosomal Sorting Complexes Required for Transport / Q000235:genetics / Q000378:metabolism*; D015683:Gene Products, gag / Q000235:genetics / Q000378:metabolism; D005816:Genetic Complementation Test; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism*; D014771:Virion / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D053586:Virus Internalization; D014779:Virus Replication; D000099177:Tsg101 Protein
D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D015683:Gene Products, gag; D020033:Protein Isoforms; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D033921:Vesicular Transport Proteins; D000099177:Tsg101 Protein; C443709:CHMP1A protein, human; C117020:PDCD6IP protein, human
Curr Opin Cell Biol. 2008 Feb;20(1):4-11
18222686
Biochem Soc Trans. 2009 Feb;37(Pt 1):195-9
19143630
J Virol. 2007 Jun;81(12):6614-22
17428861
J Virol. 2007 Jul;81(14):7380-7
17507493
Cell. 2003 Sep 19;114(6):689-99
14505569
Annu Rev Cell Dev Biol. 2007;23:519-47
17506697
J Virol. 2005 May;79(10):6134-41
15857998
Proc Natl Acad Sci U S A. 2001 Jul 3;98(14):7724-9
11427703
J Mol Biol. 2008 May 9;378(4):818-27
18395747
Virology. 2008 Sep 1;378(2):347-54
18602131
Proc Natl Acad Sci U S A. 2003 Oct 14;100(21):12414-9
14519844
J Cell Sci. 2005 Jun 15;118(Pt 12):2625-35
15914539
J Virol. 2003 Apr;77(8):4794-804
12663786
Cell. 2001 Oct 5;107(1):55-65
11595185
J Virol. 2000 Dec;74(24):11608-18
11090159
J Virol. 2007 Oct;81(20):11468-78
17686835
J Virol. 2003 Jun;77(11):6507-19
12743307
J Gen Virol. 2005 Feb;86(Pt 2):253-261
15659744
J Cell Biol. 2008 Jan 28;180(2):389-402
18209100
Cell. 2003 Sep 19;114(6):701-13
14505570
Proc Natl Acad Sci U S A. 2006 Dec 12;103(50):19140-5
17146056
Virology. 2006 Jan 5;344(1):55-63
16364736
Cell. 2007 Mar 9;128(5):841-52
17350572
J Virol. 2008 Sep;82(17):8605-18
18596102
Biochem J. 2006 Nov 15;400(1):23-32
16856878
Nature. 2009 Mar 12;458(7235):172-7
19234443
J Biol Chem. 2007 Feb 9;282(6):3847-55
17158451
Science. 2008 Sep 5;321(5894):1354-7
18687924
J Cell Sci. 2001 Jul;114(Pt 13):2395-404
11559748
J Virol. 2006 Sep;80(18):9039-52
16940516
Cell. 2009 Jan 9;136(1):97-109
19135892
J Virol. 2008 Jun;82(11):5220-33
18353951
Curr Opin Microbiol. 2006 Aug;9(4):423-9
16814597
Nat Rev Mol Cell Biol. 2007 May;8(5):355-68
17450176
J Virol. 2003 Sep;77(17):9173-82
12915533
Nat Med. 2001 Dec;7(12):1313-9
11726971
Proc Natl Acad Sci U S A. 2008 Jul 29;105(30):10541-6
18641129