Previous Article | Next Article 
Journal of Virology, January 2000, p. 834-845, Vol. 74, No. 2
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Role of Pseudorabies Virus Us9, a Type II Membrane
Protein, in Infection of Tissue Culture Cells and the Rat
Nervous System
A. D.
Brideau,1
J. P.
Card,2 and
L. W.
Enquist1,*
Department of Molecular Biology, Princeton
University, Princeton, New Jersey 08544,1 and
Departments of Neuroscience and Psychiatry, University of
Pittsburgh, Pittsburgh, Pennsylvania 152602
Received 19 July 1999/Accepted 25 October 1999
The protein product of the pseudorabies virus (PRV) Us9 gene is a
phosphorylated, type II membrane protein that is inserted into virion
envelopes and accumulates in the trans-Golgi network. It is
among a linked group of three envelope protein genes in the unique
short region of the PRV genome which are absent from the attenuated
Bartha strain. We found that two different Us9 null mutants exhibited
no obvious phenotype after infection of PK15 cells in culture. Unlike
those of gE and gI null mutants, the plaque size of Us9 null mutants on
Madin-Darby bovine kidney cells was indistinguishable from that of
wild-type virus. However, both of the Us9 null mutants exhibited a
defect in anterograde spread in the visual and cortical circuitry of
the rat. The visual system defect was characterized by restricted
infection of a functionally distinct subset of visual projections
involved in the temporal organization of behavior, whereas decreased
anterograde spread of virus to the cortical projection targets was
characteristic of animals receiving direct injections of virus into the
cortex. Spread of virus through retrograde pathways in the brain was
not compromised by a Us9 deletion. The virulence of the Us9 null
mutants, as measured by time to death and appearance of symptoms of
infection, also was reduced after their injection into the eye, but not
after cortical injection. Through sequence analysis, construction of revertants, measurement of gE and gI protein synthesis in the Us9 null
mutants, and mixed-infection studies of rats, we conclude that the
restricted-spread phenotype after infection of the rat nervous system
reflects the loss of Us9 and is not an indirect effect of the Us9
mutations on expression of glycoproteins gE and gI. Therefore, at least
three viral envelope proteins, Us9, gE, and gI, function together to
promote efficient anterograde transneuronal infection by PRV in the rat
central nervous system.
*
Corresponding author. Mailing address: Department of
Molecular Biology, Princeton University, Princeton, NJ 08544. Phone: (609) 258-2415. Fax: (609) 258-1035. E-mail:
Lenquist{at}molbiol.princeton.edu.
Journal of Virology, January 2000, p. 834-845, Vol. 74, No. 2
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
This article has been cited by other articles:
-
McGraw, H. M., Awasthi, S., Wojcechowskyj, J. A., Friedman, H. M.
(2009). Anterograde Spread of Herpes Simplex Virus Type 1 Requires Glycoprotein E and Glycoprotein I but Not Us9. J. Virol.
83: 8315-8326
[Abstract]
[Full Text]
-
Curanovic, D., Enquist, L. W.
(2009). Virion-Incorporated Glycoprotein B Mediates Transneuronal Spread of Pseudorabies Virus. J. Virol.
83: 7796-7804
[Abstract]
[Full Text]
-
Lyman, M. G., Kemp, C. D., Taylor, M. P., Enquist, L. W.
(2009). Comparison of the Pseudorabies Virus Us9 Protein with Homologs from Other Veterinary and Human Alphaherpesviruses. J. Virol.
83: 6978-6986
[Abstract]
[Full Text]
-
Snyder, A., Polcicova, K., Johnson, D. C.
(2008). Herpes Simplex Virus gE/gI and US9 Proteins Promote Transport of both Capsids and Virion Glycoproteins in Neuronal Axons. J. Virol.
82: 10613-10624
[Abstract]
[Full Text]
-
Lyman, M. G., Curanovic, D., Brideau, A. D., Enquist, L. W.
(2008). Fusion of Enhanced Green Fluorescent Protein to the Pseudorabies Virus Axonal Sorting Protein Us9 Blocks Anterograde Spread of Infection in Mammalian Neurons. J. Virol.
82: 10308-10311
[Abstract]
[Full Text]
-
Lyman, M. G., Feierbach, B., Curanovic, D., Bisher, M., Enquist, L. W.
(2007). Pseudorabies Virus Us9 Directs Axonal Sorting of Viral Capsids. J. Virol.
81: 11363-11371
[Abstract]
[Full Text]
-
Klopfleisch, R., Klupp, B. G., Fuchs, W., Kopp, M., Teifke, J. P., Mettenleiter, T. C.
(2006). Influence of pseudorabies virus proteins on neuroinvasion and neurovirulence in mice.. J. Virol.
80: 5571-5576
[Abstract]
[Full Text]
-
Lee, G. E., Murray, J. W., Wolkoff, A. W., Wilson, D. W.
(2006). Reconstitution of Herpes Simplex Virus Microtubule-Dependent Trafficking In Vitro. J. Virol.
80: 4264-4275
[Abstract]
[Full Text]
-
Chowdhury, S. I., Mahmood, S., Simon, J., Al-Mubarak, A., Zhou, Y.
(2006). The Us9 Gene of Bovine Herpesvirus 1 (BHV-1) Effectively Complements a Us9-Null Strain of BHV-5 for Anterograde Transport, Neurovirulence, and Neuroinvasiveness in a Rabbit Model. J. Virol.
80: 4396-4405
[Abstract]
[Full Text]
-
Wang, F., Tang, W., McGraw, H. M., Bennett, J., Enquist, L. W., Friedman, H. M.
(2005). Herpes Simplex Virus Type 1 Glycoprotein E Is Required for Axonal Localization of Capsid, Tegument, and Membrane Glycoproteins. J. Virol.
79: 13362-13372
[Abstract]
[Full Text]
-
Pomeranz, L. E., Reynolds, A. E., Hengartner, C. J.
(2005). Molecular Biology of Pseudorabies Virus: Impact on Neurovirology and Veterinary Medicine. Microbiol. Mol. Biol. Rev.
69: 462-500
[Abstract]
[Full Text]
-
Ch'ng, T. H., Enquist, L.W.
(2005). Neuron-to-Cell Spread of Pseudorabies Virus in a Compartmented Neuronal Culture System. J. Virol.
79: 10875-10889
[Abstract]
[Full Text]
-
Ch'ng, T. H., Enquist, L. W.
(2005). Efficient Axonal Localization of Alphaherpesvirus Structural Proteins in Cultured Sympathetic Neurons Requires Viral Glycoprotein E. J. Virol.
79: 8835-8846
[Abstract]
[Full Text]
-
Brittle, E. E., Reynolds, A. E., Enquist, L. W.
(2004). Two Modes of Pseudorabies Virus Neuroinvasion and Lethality in Mice. J. Virol.
78: 12951-12963
[Abstract]
[Full Text]
-
Klopfleisch, R., Teifke, J. P., Fuchs, W., Kopp, M., Klupp, B. G., Mettenleiter, T. C.
(2004). Influence of Tegument Proteins of Pseudorabies Virus on Neuroinvasion and Transneuronal Spread in the Nervous System of Adult Mice after Intranasal Inoculation. J. Virol.
78: 2956-2966
[Abstract]
[Full Text]
-
Clase, A. C., Lyman, M. G., del Rio, T., Randall, J. A., Calton, C. M., Enquist, L. W., Banfield, B. W.
(2003). The Pseudorabies Virus Us2 Protein, a Virion Tegument Component, Is Prenylated in Infected Cells. J. Virol.
77: 12285-12298
[Abstract]
[Full Text]
-
Banfield, B. W., Kaufman, J. D., Randall, J. A., Pickard, G. E.
(2003). Development of Pseudorabies Virus Strains Expressing Red Fluorescent Proteins: New Tools for Multisynaptic Labeling Applications. J. Virol.
77: 10106-10112
[Abstract]
[Full Text]
-
Miranda-Saksena, M., Boadle, R. A., Armati, P., Cunningham, A. L.
(2002). In Rat Dorsal Root Ganglion Neurons, Herpes Simplex Virus Type 1 Tegument Forms in the Cytoplasm of the Cell Body. J. Virol.
76: 9934-9951
[Abstract]
[Full Text]
-
Koshizuka, T., Goshima, F., Takakuwa, H., Nozawa, N., Daikoku, T., Koiwai, O., Nishiyama, Y.
(2002). Identification and Characterization of the UL56 Gene Product of Herpes Simplex Virus Type 2. J. Virol.
76: 6718-6728
[Abstract]
[Full Text]
-
Chowdhury, S. I., Onderci, M., Bhattacharjee, P. S., Al-Mubarak, A., Weiss, M. L., Zhou, Y.
(2002). Bovine Herpesvirus 5 (BHV-5) Us9 Is Essential for BHV-5 Neuropathogenesis. J. Virol.
76: 3839-3851
[Abstract]
[Full Text]
-
Diefenbach, R. J., Miranda-Saksena, M., Diefenbach, E., Holland, D. J., Boadle, R. A., Armati, P. J., Cunningham, A. L.
(2002). Herpes Simplex Virus Tegument Protein US11 Interacts with Conventional Kinesin Heavy Chain. J. Virol.
76: 3282-3291
[Abstract]
[Full Text]
-
del Rio, T., Werner, H. C., Enquist, L. W.
(2002). The Pseudorabies Virus VP22 Homologue (UL49) Is Dispensable for Virus Growth In Vitro and Has No Effect on Virulence and Neuronal Spread in Rodents. J. Virol.
76: 774-782
[Abstract]
[Full Text]
-
Demmin, G. L., Clase, A. C., Randall, J. A., Enquist, L. W., Banfield, B. W.
(2001). Insertions in the gG Gene of Pseudorabies Virus Reduce Expression of the Upstream Us3 Protein and Inhibit Cell-to-Cell Spread of Virus Infection. J. Virol.
75: 10856-10869
[Abstract]
[Full Text]
-
Billig, I., Foris, J. M., Enquist, L. W., Card, J. P., Yates, B. J.
(2000). Definition of Neuronal Circuitry Controlling the Activity of Phrenic and Abdominal Motoneurons in the Ferret Using Recombinant Strains of Pseudorabies Virus. J. Neurosci.
20: 7446-7454
[Abstract]
[Full Text]
-
Brideau, A. D., Eldridge, M. G., Enquist, L. W.
(2000). Directional Transneuronal Infection by Pseudorabies Virus Is Dependent on an Acidic Internalization Motif in the Us9 Cytoplasmic Tail. J. Virol.
74: 4549-4561
[Abstract]
[Full Text]
-
Smith, G. A., Enquist, L. W.
(2000). A self-recombining bacterial artificial chromosome and its application for analysis of herpesvirus pathogenesis. Proc. Natl. Acad. Sci. USA
97: 4873-4878
[Abstract]
[Full Text]
-
Tomishima, M.J., Enquist, L.W.
(2001). A conserved {alpha}-herpesvirus protein necessary for axonal localization of viral membrane proteins. JCB
154: 741-752
[Abstract]
[Full Text]