Functional analysis of the pseudorabies virus UL51 protein.
Homologs of the UL51 protein of herpes simplex virus have been identified in all herpesvirus subfamilies, but until now, no function has been assigned to any of them. To investigate function of the UL51 gene product of the alphaherpesvirus pseudorabies virus (PrV), we isolated and analyzed a mutant lacking the major part of the open reading frame, PrV-DeltaUL51F, and a rescuant. One-step growth analysis of PrV-DeltaUL51F revealed only slightly reduced titers, but plaque size was notably diminished and reached only approximately 30% the plaque size of wild-type PrV. Ultrastructurally, intracytoplasmic capsids were found in large numbers either without envelope or in different stages of envelopment, indicating that secondary envelopment in the cytoplasm was less efficient. However, neuroinvasion in the mouse trigeminal pathway after intranasal infection was only slightly delayed. A PrV UL11 mutant also showed a defect in secondary envelopment (M. Kopp, H. Granzow, W. Fuchs, B. G. Klupp, E. Mundt, A. Karger, and T. C. Mettenleiter, J. Virol. 77:5339-5351, 2003). Since both proteins are part of the viral tegument and are predicted to be membrane associated, they may serve similar, possibly redundant functions during viral morphogenesis. Therefore, we also isolated a mutant simultaneously lacking UL51 and UL11. This mutant exhibited further reduced plaque size compared to the single-deletion mutants, but viral titers were comparable to those for the UL11 mutant. In electron microscopic analyses, the observed defect in secondary envelopment was similar to that found in the UL11 single-deletion mutant. In conclusion, both conserved tegument proteins, either singly or in combination, are involved in virion morphogenesis in the cytoplasm but are not essential for viral replication in vitro and in vivo.
Klupp
Barbara G
BG
Institute of Molecular Biology, Friedrich-Loeffler-Institut, Boddenblick 5A, Greifswald-Insel Riems D-17493, Germany.
Granzow
Harald
H
Klopfleisch
Robert
R
Fuchs
Walter
W
Kopp
Martina
M
Lenk
Matthias
M
Mettenleiter
Thomas C
TC
D000818:Animals; D002213:Capsid / Q000648:ultrastructure; D003593:Cytoplasm / Q000821:virology; D004195:Disease Models, Animal; D011558:Herpesvirus 1, Suid / Q000235:genetics / Q000254:growth & development / Q000502:physiology*; D051379:Mice; D008854:Microscopy, Electron; D009024:Morphogenesis; D010750:Phosphoproteins / Q000235:genetics* / Q000502:physiology*; D011557:Pseudorabies / Q000473:pathology / Q000821:virology; D011817:Rabbits; D017384:Sequence Deletion; D010948:Viral Plaque Assay; D014764:Viral Proteins; D015678:Viral Structural Proteins / Q000235:genetics / Q000502:physiology; D014771:Virion / Q000648:ultrastructure
D010750:Phosphoproteins; C073414:UL11 protein, herpesviridae; C116751:UL51 protein, HSV-1; D014764:Viral Proteins; D015678:Viral Structural Proteins
J Virol. 1995 Sep;69(9):5560-7
7637001
Nature. 1970 Aug 15;227(5259):680-5
5432063
J Virol. 1999 Aug;73(8):6405-14
10400733
J Histochem Cytochem. 1981 Apr;29(4):577-80
6166661
J Virol. 1997 Jul;71(7):5635-8
9188640
J Gen Virol. 1998 Dec;79 ( Pt 12):3027-31
9880018
J Virol. 2003 May;77(9):5339-51
12692236
J Virol. 1995 Feb;69(2):825-33
7815549
J Virol. 2000 Sep;74(18):8692-9
10954570
Virus Res. 2002 Mar 20;84(1-2):125-34
11900845
J Virol. 1992 Aug;66(8):5168-74
1321297
Virus Res. 2004 Dec;106(2):167-80
15567495
Biochim Biophys Acta. 1999 Aug 12;1451(1):1-16
10446384
J Virol. 1997 Mar;71(3):2072-82
9032339
Gene. 1995 May 26;158(1):9-14
7789817
J Virol. 2000 Aug;74(15):7137-45
10888654
J Virol. 2001 Apr;75(8):3675-84
11264357
Autoimmunity. 1989;2(3):201-11
2491605
J Virol. 1995 Dec;69(12):7472-82
7494253
J Gen Virol. 1988 Jul;69 ( Pt 7):1531-74
2839594
J Virol. 2003 Mar;77(5):3204-16
12584344
J Virol. 2001 Oct;75(19):8927-36
11533156
J Virol. 2004 Mar;78(6):3024-34
14990721
Virology. 1990 Aug;177(2):684-91
2164730
J Virol. 2000 May;74(9):4004-16
10756012
Vet Res. 2000 Jan-Feb;31(1):99-115
10726640
J Gen Virol. 1992 Mar;73 ( Pt 3):539-47
1312117
J Gen Virol. 1989 Dec;70 ( Pt 12):3147-57
2558153
Nature. 1984 Jul 19-25;310(5974):207-11
6087149
Curr Top Microbiol Immunol. 1990;154:125-69
2161319
Virology. 1959 Apr;7(4):394-407
13669311
J Virol. 1999 Apr;73(4):3014-22
10074151
J Virol. 2004 Mar;78(6):2956-66
14990714
J Virol. 2003 Oct;77(19):10594-605
12970444
Proc Natl Acad Sci U S A. 2000 Jun 6;97(12):6640-5
10829079
J Virol. 2002 Feb;76(4):1537-47
11799148
Virology. 1973 Apr;52(2):456-67
4705382
J Virol. 2001 Dec;75(24):12209-19
11711612
J Virol. 2004 Jan;78(1):424-40
14671123