Previous Article | Next Article 
J Virol, May 1998, p. 4434-4441, Vol. 72, No. 5
Departments of
Neuroscience,1
Neurobiology,3 and
Psychiatry,2 University of
Pittsburgh, Pittsburgh, Pennsylvania 15260, and
Department
of Molecular Biology, Princeton University, Princeton, New Jersey
085444
Received 6 October 1997/Accepted 5 February 1998
Pseudorabies virus (PRV), a swine neurotropic alphaherpesvirus, is
known to invade the central nervous system (CNS) of a variety of animal
species through peripherally projecting axons, replicate in the parent
neurons, and then pass transsynaptically to infect other neurons of a
circuit. Studies of the human pathogen herpes simplex virus type 1 have
reported differences in the direction of transport of two strains of
this virus after direct injection into the primate motor cortex. In the
present study we examined the direction of transport of virulent and
attenuated strains of PRV, utilizing injections into the rat prefrontal
cortex to evaluate specific movement of virus through CNS circuitry.
The data demonstrate strain-dependent patterns of infection consistent with bidirectional (anterograde and retrograde) transport of virulent virus and unidirectional (retrograde) transport of attenuated PRV from
the site of injection. The distribution of infected neurons and the
extent of transsynaptic passage also suggest that a release defect in
the attenuated strain reduces the apparent rate of viral transport
through neuronal circuitry. Finally, injection of different concentrations of virus influenced the onset of replication within a
neural circuit. Taken together, these data suggest that viral envelope
glycoproteins and virus concentration at the site of injection are
important determinants of the rate and direction of viral transport
through a multisynaptic circuit in the CNS.
Considerable insight into the
neurotropism of alphaherpesviruses has been gained from examination of
the invasiveness and replication of different strains of virus in
experimental animals. For example, analysis of the invasiveness of
various strains of the swine pathogen pseudorabies virus (PRV) have
demonstrated strain-dependent patterns of infection of the central
nervous system (CNS) after peripheral inoculation. In the visual
system, these differences are manifested by differential replication of attenuated strains of virus in functionally distinct circuits. After
intravitreal injection, virulent PRV infects all retinorecipient regions of the brain in two temporally separated waves of infection, while isogenic strains that contain selective deletions of genes encoding the gI and gE envelope glycoproteins produce restricted infections of components of this circuitry involved in the regulation of circadian timing (10, 12, 17, 45). Similar findings have
been reported in rat cardiac circuitry after injection of the same
strains of PRV into the heart (40, 41), and a number of
investigators have reported more restricted patterns of infection than
that of the wild-type virus after identical injection of attenuated
strains of PRV or other viruses into a variety of sites (1-3, 19,
23-25, 31, 32, 36, 37). A common theme that has emerged from
these studies is that defects in one or more envelope glycoprotein
genes can not only alter the invasiveness and/or replication of these
viruses but also reduce virulence.
The ability of neurotropic alphaherpesviruses to pass transsynaptically
has led to the increasing use of these viruses for analysis of neuronal
circuitry (see references 9, 15, 26, 29, and
44 for recent reviews). Most investigations have
introduced viruses into select populations of peripherally projecting
neurons by inoculating their synaptic targets and then followed the
progressive retrograde movement of the virus through multisynaptic
circuits impinging upon these first-order neurons. Fewer studies have
examined patterns of viral infection after direct injection of virus
into the CNS (3, 20, 22, 28, 33-35, 46). One such study
compared the patterns of infection produced by injection of two strains of herpes simplex virus type 1 into the motor strip of the primate cortex (46). These investigators reported that the
McIntyre-B strain was transported transneuronally only in the
retrograde direction, while identical injection of the H129 strain
produced a pattern of infection consistent only with anterograde
transneuronal passage. Further support for selective anterograde
transneuronal infection by the H129 strain in the CNS has recently been
reported in the murine visual system (42) and
thalamocortical projection systems infected by tooth pulp inoculation
(4). In the present study we sought to determine if
strain-dependent patterns of infection could be achieved by injection
of different strains of PRV into the rat prefrontal cortex (PFC).
(Early experiments included in this report were presented at a meeting
of the Society for Neuroscience [16].)
To address this question, we injected virulent or attenuated PRV into
the PFC and analyzed the distribution of infected neurons throughout
the brain at postinoculation intervals extending to 68 h (Table
1). The PFC was selected because it
possesses a well-characterized circuitry in which the direction of
viral transport from the site of injection can be unambiguously
evaluated (Fig. 1). Neurons in this
region project to the striatum but do not receive reciprocal projections from the same area (7, 18, 39). Therefore, the
appearance of infected neurons in the striatum at short survival times
provides direct evidence that the virus replicated in PFC neurons and
was transported in an anterograde direction to produce a transsynaptic
infection of striatal neurons. The PFC also shares reciprocal
projections with a variety of regions, including the perirhinal cortex
(Fig. 1). Neurons in lamina V of the perirhinal cortex are known to
give rise to a dense projection to laminae I, II, and VI of the PFC
(27), and therefore, this circuit provides an accurate
measure of retrograde infection. However, the PFC also projects to the
perirhinal cortex and elaborates an axonal arbor that terminates in
both superficial and deep laminae (13). Thus, anterograde
transsynaptic passage of virus would infect a more widely distributed
group of perirhinal neurons than the restricted infection of lamina V
that results from retrograde transport of virus from the PFC. In our
experimental model, if the perirhinal cortex were being infected by
bidirectional transport of virus, the need to replicate virus in the
PFC prior to anterograde transport and the previous demonstration that
retrograde transport of PRV is faster than anterograde transport
(11) predict that retrograde infection of lamina V
would precede the more widespread anterograde infection of other
laminae in the perirhinal cortex. Therefore, analysis of the
distribution of infected neurons in this region at various
postinoculation intervals provides a further stringent test of the
anterograde versus the retrograde route of viral infection.
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Different Patterns of Neuronal Infection after
Intracerebral Injection of Two Strains of Pseudorabies Virus
ABSTRACT
Top
Abstract
Text
References
TEXT
Top
Abstract
Text
References
TABLE 1.
Experimental groups
View larger version (71K):
[in a new window]
FIG. 1.
Organization of the brain circuitry that was the subject
of this analysis. Virus was injected into the PFC at level A. In the
majority of cases the cannula tract passed vertically through
intermediate layers of the anterior cingulate and prelimbic cortex; in
a few instances the cannula extended further ventrally into the
infralimbic cortex. All of these regions contain neurons that give rise
to a dense axonal projection to the striatum (level B). This
monosynaptic projection is not reciprocated, creating an ideal means of
determining if the virus is being transported in an anterograde
direction to produce a transsynaptic infection. The perirhinal cortex
is among a large group of structures that maintain reciprocal
connections with the PFC (level C). Neurons in the PFC give rise to
axons that terminate in both superficial and deep layers of the
perirhinal cortex. Therefore, an anterograde transsynaptic infection
would be characterized by a multilaminar distribution of
PRV-immunoreactive neurons. In contrast, the reciprocal projection of
the perirhinal cortex to the PFC arises predominantly from lamina V. Therefore, retrograde transport of virus from the PFC would produce a
selective infection of this layer of the perirhinal cortex. The boxed
areas in levels D and E illustrate the location of the raphe nucleus
and locus coeruleus illustrated in Fig. 3. See the text for further
details on the organization of this circuitry. The templates used in
this figure were modified from reference 43.
We selected the Becker (PRV-Becker [6]) and Bartha (PRV-Bartha [5]) strains of PRV for this comparative analysis. PRV-Becker is a virulent wild-type isolate, while PRV-Bartha is an attenuated vaccine strain harboring a variety of mutations (29). One well-characterized mutation in PRV-Bartha is a deletion in the unique short region of the viral genome that eliminates genes encoding the gE and gI envelope glycoproteins. This strain also carries several mutations in the gC gene, including a signal sequence mutation that reduces the concentration of this glycoprotein in viral and host cell membranes. We have previously shown that PRV-Bartha only infects a subset of the visual pathways that are permissive to PRV-Becker replication (10, 12, 17, 45). In the present study we entertained the hypothesis that, after central injection, PRV-Bartha would produce a more restricted pattern of infection than that produced by identical injection of PRV-Becker and that this pattern would reflect the elimination of any infection produced by anterograde transport of the virus from the site of injection.
The experiments were conducted in the following manner. Adult male
Sprague-Dawley albino rats, housed in a 12-12-h light-dark cycle, were
anesthetized with ketamine (60 mg/kg of body weight) and xylazine (7 mg/kg) and placed in a stereotaxic frame (Stoelting Co., Wood Dale,
Ill.) to secure the cranium. An incision was made in the scalp and a
hole was drilled in the skull at the desired site of injection. The
location of the injection site in the PFC was standardized between
animals by using stereotaxic coordinates (AP = +2.5; ML = +0.25; DV = 
4.0 from the skull, with the mouthpiece at 3.3)
taken from reference 43. Virus (100 or 200 nl/animal [Table 1]) was injected through a 1-µl Hamilton syringe at a rate
of 10 nl/min, and the needle was left in situ for 5 min following completion of the injection to reduce reflux of the inoculum up the
cannula tract. Fourteen animals were injected with PRV-Becker and
killed 24 to 49 h after injection. Sixteen animals were injected with PRV-Bartha and killed 24 to 68 h after injection. After the appropriate postinoculation interval, the animals were anesthetized and
sacrificed by transcardiac perfusion fixation with buffered aldehyde
solutions and procedures described previously (15). The
brains were then removed, postfixed, cryoprotected, and sectioned serially in the coronal plane at 35 µm/section with a freezing microtome. Sections at a frequency of 210 µm (every sixth
section) were processed for immunohistochemical localization
of viral antigens with a rabbit polyclonal antiserum generated against
acetone-inactivated PRV (11) and affinity-purified donkey
anti-rabbit immunoglobulin G (Jackson ImmunoResearch, Inc.), using the
avidin-biotin modification of the immunoperoxidase procedure
(21) (reagents from Vector Laboratories). The
processed sections were mounted on gelatin-coated slides,
dehydrated, cleared, and coverslipped. Specific details regarding
the application of this procedure in our laboratory have been
published previously (15). The material was analyzed and
digitized with a Zeiss Axioplan microscope and a Simple32 image
analysis system (C-Imaging Systems).
In all cases, the distribution of infected neurons was consistent with the established projections of the PFC and there was no evidence for nonsynaptic spread of virus within the time course analyzed. We focused upon the pattern of infection in the striatum and perirhinal cortex, but the conclusions are drawn from analysis of the full pattern of infection in each brain. Comparison of the infections produced by identical injection of PRV-Becker and PRV-Bartha revealed marked differences in the cellular distribution of viral antigens, as well as the resulting patterns of CNS infection. Additionally, injection of different concentrations of the same virus altered the time course of infection. Three general conclusions can be drawn from the data. First, injection of high concentrations of virus produced an earlier onset of viral replication than lower concentrations of the same strain. Second, neurons infected by PRV-Bartha exhibited a much more extensive intracellular distribution of viral antigens than those infected by PRV-Becker, even when PRV-Becker-infected animals, which survived a long time, were compared to PRV-Bartha-infected animals, which survived only a short time. Third, PRV-Becker produced a pattern of infection consistent with bidirectional (anterograde and retrograde) transport of virus from the injection site, whereas PRV-Bartha only replicated within neurons projecting to the injection site (retrograde transport). The evidence for strain-specific transport of PRV-Becker and PRV-Bartha will be discussed first, as this information is fundamental to the interpretation of the data supporting the other findings.
Direction of viral transport from the injection site. The striatum provided the most clear-cut test of directional specificity of viral transport. As noted previously, this region receives a direct projection from the PFC but does not give rise to a reciprocal projection. Furthermore, there is a differential distribution of PFC afferents in the striatum, located mostly in the rostral, dorsal, and centromedial zones (7, 18, 39), providing a further rigorous means of evaluation of the specificity of transsynaptic infection. PRV-Becker produced anterograde transsynaptic infection of neurons in the striatum, and the distribution of these cells was coextensive with the previously documented distribution of the PFC afferents in the striatum (Fig. 2). Scattered infected neurons in the rostral striatal quadrant were apparent as early as 24 h after injection of PRV-Becker into the PFC (Fig. 2A and B), and the number of infected cells increased progressively with longer survival (Fig. 2C and D). Neurons exhibiting morphology consistent with medium spiny projection neurons and the larger interneurons were present at all survival intervals. These neurons differ not only in size but also in neurochemical phenotype (interneurons are cholinergic, while the projection neurons contain the inhibitory neurotransmitter GABA). We did not characterize the neurochemical phenotypes of infected neurons in this study, but the morphological distinctions in the infected neurons (Fig. 2B and D) made it clear that both cell populations were involved. Minimal cytopathic changes were apparent in striatal neurons in the longest-surviving animals, but there was no evidence of necrotic spread of infection at survival intervals extending to 48 h (Fig. 2D).
|
|
|
Intracellular distribution of viral antigens. Comparison of PRV-Becker- and PRV-Bartha-infected neurons revealed a remarkable difference in the intracellular distribution of viral antigens. Even at long postinoculation intervals, viral immunoreactivity was confined to the cell soma and proximal dendrites of neurons infected with PRV-Becker. In contrast, viral immunoreactivity was widely distributed throughout the cells and dendritic processes of neurons at shorter postinoculation intervals following PRV-Bartha infection. This was particularly apparent in the polarized pyramidal cells of the perirhinal cortex (Fig. 5). These cells characteristically exhibit a triangular cell body that gives rise to extensive dendritic arbors. The apical dendritic processes of these cells are quite long and can extend to the surface of the brain even when the cell bodies are located in deep cortical laminae. Figure 5A illustrates a number of infected neurons in lamina V of the perirhinal cortex 45 h after injection of PRV-Becker into the PFC. Viral immunoreactivity, although dense, is confined to the cell body and proximal dendrites. Neurons from the same region 36 h after PRV-Bartha injection exhibit a dramatically different intracellular distribution of viral antigen. In spite of the shorter postinoculation survival, viral antigen is densely distributed throughout the processes of the infected cells and extends into the most distal processes of the apical dendrites (Fig. 5B).
|
Effect of viral concentration. A comparison of the progression of infection after injection of different volumes of the same strain of virus into the PFC demonstrated that there was an earlier onset of PRV replication in animals injected with higher concentrations of virus. This was clearly apparent in comparing the patterns of infection in the perirhinal cortex following injection of 100 or 200 nl of PRV-Becker into the PFC. As previously described, injection of 200 nl of virus led to an early infection of layer V pyramidal neurons (Fig. 4A) followed by an extensive infection of neurons across cortical laminae at 48 h (Fig. 4B). In contrast, injection of half that volume of virus led to a delay in the onset of infection such that the magnitude of infection observed 48 h after injection of 100 nl (Fig. 4C) was equivalent to that produced at 24 h after injection of 200 nl (Fig. 4A). The present data set does not allow us to determine whether this delay resulted from the reduction in viral concentration or the reduced volume. However, in other experiments involving intrastriatal injection of PRV-Bartha we have demonstrated that concentration rather than volume is the important variable that determines the onset of production of infectious progeny in a permissive neuron (35).
The substantial differences observed in the patterns and progression of infection after intracerebral injection of PRV-Becker and PRV-Bartha are consistent with the strain-dependent differences in viral replication observed in other studies. Although many studies have demonstrated retrograde transsynaptic infections of the CNS with a variety of alphaherpesvirus strains, only a few have reported anterograde transsynaptic infections (3, 4, 42, 46). Zemanick and colleagues (46) reported strain-specific transport of two strains of herpes simplex virus type 1 injected into the motor strip of the primate cortex, with the H129 strain moving selectively in the anterograde direction. Further evidence in support of anterograde transneuronal infection of H129 has recently been provided by Sun and coworkers (42), who demonstrated anterograde transneuronal infection of the lateral geniculate nucleus and striate cortex after intravitreal injection of this strain, and Barnett and colleagues reported anterograde transneuronal infection in the CNS after inoculation of the tooth pulp with this strain (4). Our data differ from these reports in that we observed bidirectional transport of PRV-Becker and unidirectional retrograde transport of PRV-Bartha rather than selective anterograde transneuronal passage of either strain. The mechanisms underlying the directional specificity of H129 have not been established, but it is likely that the differences noted in our analysis may be related to the well-characterized alterations in the viral genome that distinguish PRV-Bartha from PRV-Becker. Prior studies have demonstrated that the absence of envelope glycoprotein genes can profoundly alter the invasiveness and/or spread of PRV. For example, gB and gD have both been shown to be essential for entry of virus into neurons, but only gB is necessary for subsequent transsynaptic passage (1, 19, 31, 36). Prominent roles for the gE and gI glycoproteins have also been demonstrated. We have shown that mutants isogenic with PRV-Becker that lack gE, gI, or both of these gene products produce a restricted pattern of infection of a functionally distinct component of the visual circuitry (10, 12, 17, 45). These findings are similar to data demonstrating altered invasiveness of PRV through olfactory or trigeminal circuitry in pigs after intranasal inoculation (24, 31, 32) and support a role for these virally encoded gene products in anterograde transneuronal passage. We are currently testing gE and gI mutants in the PFC paradigm and predict that these studies will demonstrate that the absence of these genes eliminates the anterograde component of the infection. In summary, we have demonstrated distinct differences in the patterns of infection produced by two strains of PRV, in terms of both the direction of transport and the intracellular distribution of viral antigens. Deletions in the viral genome documented for the strain with the more restricted phenotype, PRV-Bartha, suggest that these alterations may be due to the absence of one or more viral envelope glycoproteins in the unique short region of the viral genome.| |
ACKNOWLEDGMENTS |
|---|
We gratefully acknowledge the technical assistance of Jen-Shew Yen and Marlies Eldridge.
This work was supported by NIH RO1s MH53574 (J.P.C.), MH45507 (P.L.), and NINDS33506 (L.W.E.).
| |
FOOTNOTES |
|---|
* Corresponding author. Mailing address: Department of Neuroscience, 446 Crawford Hall, University of Pittsburgh, Pittsburgh, PA 15260. Phone: (412) 624-6995. Fax: (412) 624-9198. E-mail: Card{at}bns.pitt.edu.
| |
REFERENCES |
|---|
|
Top
Abstract
Text
References
|
|---|
| 1. |
Babic, N.,
T. C. Mettenleiter,
A. Flamand, and G. Ugolini.
1993.
Role of essential glycoproteins gII and gp50 in transneuronal transfer of pseudorabies virus from the hypoglossal nerves of mice.
J. Virol.
67:4421-4426 |
| 2. | Babic, N., B. Klupp, A. Brack, T. C. Mettenleiter, G. Ugolini, and A. Flamand. 1996. Deletion of glycoprotein gE reduces the propagation of pseudorabies virus in the nervous system of mice after intranasal inoculation. Virology 219:279-284[Medline]. |
| 3. | Barnett, E. M., M. D. Cassell, and S. Perlman. 1993. Two neurotropic viruses, herpes simplex virus type 1 and mouse hepatitis virus, spread along different neural pathways from the main olfactory bulb. Neuroscience 57:1007-1025[Medline]. |
| 4. | Barnett, E. M., G. D. Evans, N. Sun, S. Perlman, and M. D. Cassell. 1995. Anterograde tracing of trigeminal afferent pathways from the murine tooth pulp to cortex using herpes simplex virus type 1. J. Neurosci. 15:2972-2984[Abstract]. |
| 5. | Bartha, A. 1961. Experimental reduction of virulence of Aujeszky's disease virus. Magy. Allatorv. Lapja 16:42-45. |
| 6. | Becker, C. H. 1967. Zur primaren Schadingung vegetativer Ganglien nach Infektion mit deme Herpes suis Virus bei verschiedenen Tierarten. Experientia 23:209-217[Medline]. |
| 7. | Beckstead, R. M. 1979. An autoradiographic examination of corticocortical and subcortical projections of the mediodorsal-projection (prefrontal) cortex in the rat. J. Comp. Neurol. 184:43-62[Medline]. |
| 8. |
Ben-Porat, T.,
J. DeMarchi,
J. Pendrys,
R. A. Veach, and A. S. Kaplan.
1986.
Proteins specified by the short unique region of the genome of pseudorabies virus play a role in the release of virions from certain cells.
J. Virol.
57:191-196 |
| 9. | Card, J. P., and P. L. Strick. 1992. Transneuronal mapping of neural circuits with alpha herpesviruses, p. 81-101. In J. P. Bolam (ed.), Experimental neuroanatomy, a practical approach. IRL Press, Oxford, England. |
| 10. |
Card, J. P.,
M. E. Whealy,
A. K. Robbins, and L. W. Enquist.
1992.
Pseudorabies virus envelope glycoprotein gI influences both neurotropism and virulence during infection of the rat visual system.
J. Virol.
66:3032-3041 |
| 11. | Card, J. P., L. Rinaman, J. S. Schwaber, R. R. Miselis, M. E. Whealy, A. K. Robbins, and L. W. Enquist. 1990. Neurotropic properties of pseudorabies virus: uptake and transneuronal passage in the rat central nervous system. J. Neurosci. 10:1974-1994[Abstract]. |
| 12. | Card, J. P., M. E. Whealy, A. K. Robbins, R. Y. Moore, and L. W. Enquist. 1991. Two alpha herpesvirus strains are transported differentially in the rodent visual system. Neuron 6:957-969[Medline]. |
| 13. | Deacon, T. W., H. Eichenbaum, P. Rosenberg, and K. W. Eckman. 1983. Afferent connections of the perirhinal cortex in the rat. J. Comp. Neurol. 220:168-190[Medline]. |
| 14. | Enquist, L. W. 1994. Infection of the mammalian nervous system by pseudorabies virus. Semin. Virol. 5:221-231. |
| 15. | Enquist, L. W., and J. P. Card. 1996. Pseudorabies virus: a tool for tracing neuronal connections, p. 333-348. In P. R. Lowenstein, and L. W. Enquist (ed.), Protocols for gene transfer in neuroscience: towards gene therapy of neurological disorders. John Wiley & Sons, Inc., New York, N.Y. |
| 16. | Enquist, L. W., P. Levitt, and J. P. Card. 1993. Connections of the adult rat prefrontal cortex revealed by intracerebral injection of a swine alpha herpesvirus. Soc. Neurosci. Abstr. 19:589.11. |
| 17. |
Enquist, L. W.,
J. Dubin,
M. E. Whealy, and J. P. Card.
1994.
Complementation analysis of pseudorabies virus gE and gI mutants in retinal ganglion cell neurotropism.
J. Virol.
68:5275-5279 |
| 18. |
Gerfen, C. R.
1989.
The neostriatal mosaic: striatal patch-matrix organization is related to cortical lamination.
Science
246:385-388 |
| 19. |
Heffner, S.,
F. Kovács,
B. G. Klupp, and T. C. Mettenleiter.
1993.
Glyco-protein gp50-negative pseudorabies virus: a novel approach toward a nonspreading live herpesvirus vaccine.
J. Virol.
67:1529-1537 |
| 20. |
Hoover, J. E., and P. L. Strick.
1993.
Multiple output channels in the basal ganglia.
Science
259:819-821 |
| 21. | Hsu, S. M., L. Raine, and H. Fanger. 1981. The use of avidin-biotin-peroxidase complex in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J. Histochem. Cytochem. 29:577-580[Abstract]. |
| 22. |
Jasmin, L.,
A. R. Burkey,
J. P. Card, and A. Basbaum.
1997.
Transneuronal labeling of a nociceptive pathway, the spino-(trigemino-)parabrachio-amygdaloid, in the rat.
J. Neurosci.
17:3751-3765 |
| 23. |
Kimman, T. G.,
N. de Wind,
N. Oei-Lie,
J. M. A. Pol,
A. J. M. Berns, and A. L. J. Gielkens.
1992.
Contribution of single genes within the unique short region of Aujeszky's disease virus (suid herpesvirus type 1) to virulence, pathogenesis and immunogenicity.
J. Gen. Virol.
73:243-251 |
| 24. |
Kritas, S. K.,
M. B. Pensaert, and T. C. Mettenleiter.
1994.
Role of envelope glycoproteins gI, gp63 and gIII in the invasion and spread of Aujeszky's disease virus in the olfactory nervous pathway of the pig.
J. Gen. Virol.
75:2319-2327 |
| 25. | Lafay, F., P. Coulon, L. Astic, D. Saucier, D. Riche, A. Holley, and A. Flamand. 1991. Spread of the CVS strain of rabies virus and of the avirulent mutant AvO1 along the olfactory pathways of the mouse after intranasal inoculation. Virology 183:320-330[Medline]. |
| 26. | Loewy, A. D. 1995. Pseudorabies virus: a transneuronal tracer for neuroanatomical studies, p. 349-366. In M. G. Kaplitt, and A. D. Loewy (ed.), Viral vectors. Academic Press, San Diego, Calif. |
| 27. | McIntyre, D. C., M. E. Kelly, and W. A. Staines. 1996. Efferent projections of the anterior perirhinal cortex in the rat. J. Comp. Neurol. 369:302-318[Medline]. |
| 28. | McLean, J. H., M. T. Shipley, and D. Bernstein. 1989. Golgi-like transneuronal retrograde labeling with CNS injections of herpes simplex virus type 1. Brain Res. Bull. 22:867-881[Medline]. |
| 29. | Mettenleiter, T. C. 1995. Molecular properties of alphaherpesviruses used in transneuronal pathway tracing, p. 367-393. In M. G. Kaplitt, and A. D. Loewy (ed.), Viral vectors. Academic Press, San Diego, Calif. |
| 30. |
Mettenleiter, T. C.,
C. Schreurs,
F. Zuckermann, and T. Ben-Porat.
1987.
Role of pseudorabies virus glycoprotein gI in virus release from infected cells.
J. Virol.
61:2764-2769 |
| 31. | Mulder, W., J. Pol, T. Kimman, G. Kok, J. Priem, and B. Peeters. 1996. Glycoprotein D-negative pseudorabies virus can spread transneuronally via direct neuron-to-neuron transmission in its natural host, the pig, but not after additional inactivation of gE or gI. J. Virol. 70:2191-2200[Abstract]. |
| 32. |
Mulder, W. A. M.,
L. Jacobs,
J. Priem,
G. L. Kok,
F. Wagenaar,
T. G. Kimman, and J. M. A. Pol.
1994.
Glycoprotein gE-negative virus has a reduced capability to infect second- and third-order neurons of the olfactory and trigeminal routes in the porcine nervous system.
J. Gen. Virol.
75:3095-3106 |
| 33. | Norgren, R., and M. N. Lehman. 1989. Retrograde transneuronal transport of herpes simplex virus in the retina after injection in the superior colliculus, hypothalamus and optic chiasm. Brain Res. 479:374-378[Medline]. |
| 34. |
O'Donnell, P. O.,
A. Lavin,
L. W. Enquist,
A. A. Grace, and J. P. Card.
1997.
Interconnected parallel circuits between rat nucleus accumbens and thalamus revealed by retrograde transsynaptic transport of pseudorabies virus.
J. Neurosci.
17:2143-2167 |
| 35. | Park, J., L. W. Enquist, R. Y. Moore, and J. P. Card. 1996. The effect of viral concentration upon invasiveness, replication, and transsynaptic passage of pseudorabies virus injected into striatum. Soc. Neurosci. Abstr. 22:1730. |
| 36. |
Peeters, B.,
J. Pol,
A. Gielkens, and R. Moormann.
1993.
Envelope glycoprotein gp50 of pseudorabies virus is essential for virus entry but is not required for viral spread in mice.
J. Virol.
67:170-177 |
| 37. | Pol, J. M. A., A. L. J. Gielkens, and J. T. van Oirschot. 1989. Comparative pathogenesis of three strains of pseudorabies virus in pigs. Microb. Pathog. 7:361-371[Medline]. |
| 38. |
Schreurs, C.,
T. C. Mettenleiter,
F. Zuckermann,
N. Sugg, and T. Ben-Porat.
1988.
Glycoprotein gIII of pseudorabies virus is multifunctional.
J. Virol.
62:2251-2257 |
| 39. | Sesack, S. R., A. Y. Deutch, R. H. Roth, and B. S. Bunney. 1989. Togographical organization of the medial prefrontal cortex in the rat: an anterograde tract-tracing study with phaseolus vulgaris leucoagglutinin. J. Comp. Neurol. 290:213-242[Medline]. |
| 40. |
Standish, A.,
L. W. Enquist, and J. S. Schwaber.
1994.
Innervation of the heart and its central medullary origin defined by viral tracing.
Science
263:232-234 |
| 41. | Standish, A., L. W. Enquist, J. A. Escardo, and J. S. Schwaber. 1995. Central neuronal circuit innervating the rat heart defined by transneuronal transport of pseudorabies virus. J. Neurosci. 15:1998-2012[Abstract]. |
| 42. |
Sun, N.,
M. D. Cassell, and S. Perlman.
1996.
Anterograde, transneuronal transport of herpes simplex virus type 1 strain H129 in the murine visual system.
J. Virol.
70:5405-5413 |
| 43. | Swanson, L. W. 1992. In Brain maps: structure of the rat brain. Elsevier Science Publishers B. V., Amsterdam, The Netherlands. |
| 44. | Ugolini, G. 1995. Transneuronal tracing with alpha-herpesviruses: a review of the methodology, p. 293-317. In M. G. Kaplitt, and A. D. Loewy (ed.), Viral vectors. Academic Press, San Diego, Calif. |
| 45. |
Whealy, M. E.,
J. P. Card,
A. K. Robbins,
J. R. Dubin,
H.-J. Rziha, and L. W. Enquist.
1993.
Specific pseudorabies virus infection of the rat visual system requires both gI and gp63 glycoproteins.
J. Virol.
67:3786-3797 |
| 46. |
Zemanick, M. C.,
P. L. Strick, and R. D. Dix.
1991.
Direction of transneuronal transport of herpes simplex virus 1 in the primate motor system is strain dependent.
Proc. Natl. Acad. Sci. USA
88:8048-8051 |
| 47. |
Zsak, L.,
T. C. Mettenleiter,
N. Sugg, and T. Ben-Porat.
1989.
Release of pseudorabies virus from infected cells is controlled by several viral functions and is modulated by cellular components.
J. Virol.
63:5475-5477 |
J Virol, May 1998, p. 4434-4441, Vol. 72, No. 5
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
This article has been cited by other articles:
-
Aston-Jones, G., Zhu, Y., Card, J. P.
(2004). Numerous GABAergic Afferents to Locus Ceruleus in the Pericerulear Dendritic Zone: Possible Interneuronal Pool. J. Neurosci.
24: 2313-2321
[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] -
Sawtell, N. M.
(2003). Quantitative Analysis of Herpes Simplex Virus Reactivation In Vivo Demonstrates that Reactivation in the Nervous System Is Not Inhibited at Early Times Postinoculation. J. Virol.
77: 4127-4138
[Abstract] [Full Text] -
Pickard, G. E., Smeraski, C. A., Tomlinson, C. C., Banfield, B. W., Kaufman, J., Wilcox, C. L., Enquist, L. W., Sollars, P. J.
(2002). Intravitreal Injection of the Attenuated Pseudorabies Virus PRV Bartha Results in Infection of the Hamster Suprachiasmatic Nucleus Only by Retrograde Transsynaptic Transport via Autonomic Circuits. J. Neurosci.
22: 2701-2710
[Abstract] [Full Text] -
van den Pol, A. N., Dalton, K. P., Rose, J. K.
(2002). Relative Neurotropism of a Recombinant Rhabdovirus Expressing a Green Fluorescent Envelope Glycoprotein. J. Virol.
76: 1309-1327
[Abstract] [Full Text] -
Bartness, T. J., Song, C. K., Demas, G. E.
(2001). SCN Efferents to Peripheral Tissues: Implications for Biological Rhythms. J Biol Rhythms
16: 196-204
[Abstract] -
Card, J. P.
(2000). Pseudorabies Virus and the Functional Architecture of the Circadian Timing System. J Biol Rhythms
15: 453-461
[Abstract] -
Husak, P. J., Kuo, T., Enquist, L. W.
(2000). Pseudorabies Virus Membrane Proteins gI and gE Facilitate Anterograde Spread of Infection in Projection- Specific Neurons in the Rat. J. Virol.
74: 10975-10983
[Abstract] [Full Text] -
Saldanha, C. E., Lubinski, J., Martin, C., Nagashunmugam, T., Wang, L., van der Keyl, H., Tal-Singer, R., Friedman, H. M.
(2000). Herpes Simplex Virus Type 1 Glycoprotein E Domains Involved in Virus Spread and Disease. J. Virol.
74: 6712-6719
[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] -
Carr, D. B., Sesack, S. R.
(2000). Projections from the Rat Prefrontal Cortex to the Ventral Tegmental Area: Target Specificity in the Synaptic Associations with Mesoaccumbens and Mesocortical Neurons. J. Neurosci.
20: 3864-3873
[Abstract] [Full Text] -
Tirabassi, R. S., Enquist, L. W.
(2000). Role of the Pseudorabies Virus gI Cytoplasmic Domain in Neuroinvasion, Virulence, and Posttranslational N-Linked Glycosylation. J. Virol.
74: 3505-3516
[Abstract] [Full Text] -
Gerdts, V., Beyer, J., Lomniczi, B., Mettenleiter, T. C.
(2000). Pseudorabies Virus Expressing Bovine Herpesvirus 1 Glycoprotein B Exhibits Altered Neurotropism and Increased Neurovirulence. J. Virol.
74: 817-827
[Abstract] [Full Text] -
Brideau, A. D., Card, J. P., Enquist, L. W.
(2000). Role of Pseudorabies Virus Us9, a Type II Membrane Protein, in Infection of Tissue Culture Cells and the Rat Nervous System. J. Virol.
74: 834-845
[Abstract] [Full Text] -
Kim, J.-S., Enquist, L. W., Card, J. P.
(1999). Circuit-Specific Coinfection of Neurons in the Rat Central Nervous System with Two Pseudorabies Virus Recombinants. J. Virol.
73: 9521-9531
[Abstract] [Full Text] -
Yang, M., Card, J. P., Tirabassi, R. S., Miselis, R. R., Enquist, L. W.
(1999). Retrograde, Transneuronal Spread of Pseudorabies Virus in Defined Neuronal Circuitry of the Rat Brain Is Facilitated by gE Mutations That Reduce Virulence. J. Virol.
73: 4350-4359
[Abstract] [Full Text]
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Copyright © 2009 by the American Society for Microbiology. For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»