Characterization of transsynaptic tracing with central application of pseudorabies virus

Chen, Sheng; Yang, Ming; Miselis, Richard R.; Aston‐Jones, Gary

doi:10.1016/s0006-8993(99)01680-7

Cited by 56 publications

(43 citation statements)

References 32 publications

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“…Intraocular PRV injection has been used to define central presympathetic neuronal pathways (18), and recordings can readily be made from these systems. Viral transsynaptic tracing has also been used extensively to identify anatomical circuits controlling visceral function (22,34) and can identify multisynaptic connections with specific brain regions (3,4). Combining EGFP identification with viral transneuronal labeling of multisynaptic pathways, as demonstrated in this study, is a powerful and potentially important technique for examining synaptic electrophysiology in functionally identified neural circuits.…”

Section: Discussionmentioning

confidence: 95%

“…In particular, the attenuated vaccine strain of pseudorabies virus (PRV-Bartha) has been used successfully as a self-amplifying neural tracer after peripheral application or direct injection into brain parenchyma (2)(3)(4). The usefulness of PRV as a neural tracer relies on its ability to infect chains of hierarchically connected neurons via specific transsynaptic passage of progeny virus rather than infection by lytic release into the extracellular space (4,5).…”

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confidence: 99%

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Pseudorabies virus expressing enhanced green fluorescent protein: A tool for in vitro electrophysiological analysis of transsynaptically labeled neurons in identified central nervous system circuits

Smith

Banfield

Smeraski

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

212

205

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PRV-Bartha ͉ PRV 152 ͉ suprachiasmatic nucleus ͉ retinal ganglion cell T he use of neurotropic alphaherpesviruses has greatly advanced our ability to visualize ensembles of neurons that contribute to multisynaptic circuits in the central nervous system (CNS) (1). In particular, the attenuated vaccine strain of pseudorabies virus (PRV-Bartha) has been used successfully as a self-amplifying neural tracer after peripheral application or direct injection into brain parenchyma (2-4). The usefulness of PRV as a neural tracer relies on its ability to infect chains of hierarchically connected neurons via specific transsynaptic passage of progeny virus rather than infection by lytic release into the extracellular space (4, 5). Typically, PRV infects the CNS by invading neurons in the periphery and then replicating and spreading to the CNS via synaptically linked neurons. However, PRV can also invade neurons through their somata if the viral concentration is sufficient (6), as evidenced by primary infection of retinal ganglion cells (RGCs) after intravitreal injection of PRV (7-9). Infection of RGCs with PRV-Bartha, followed by viral replication, results in the anterograde transsynaptic infection of a restricted set of retinorecipient neurons [i.e., suprachiasmatic nucleus (SCN), intergeniculate leaflet (IGL), pretectum (PT), and lateral terminal nucleus]. Intravitreal injection of the wild-type virus, PRV-Becker, produces transneuronal infection of neurons in all retinorecipient subcortical regions (7). The factors that determine the specificity of PRV-Bartha infection of selective retinorecipient targets are not completely understood, although deletion of specific genes in PRV-Becker results in a restricted neurotropism identical to that demonstrated with PRV-Bartha (10).Although viral transsynaptic tracing represents an important methodological advance for the analysis of CNS circuits, functional analysis of virus-infected neurons has been limited to sensory or sympathetic ganglia in culture (11, 12) because of the inability to identify virus-infected neurons in situ. Analyses of electrophysiological properties of neurons, in the context of known functional connections of the recorded neuron, would represent a further important methodological advance for the analysis of CNS circuits.The development of retrogradely transported fluorescent tracers has allowed investigators to examine the physiology of neurons with known projections (13-15). However, such studies usually require direct and accurate injection of a target region followed by retrograde transport to identify first-order neurons projecting to the target. Other ''prelabeling'' studies have used constructs of green fluorescent protein to label neurons that possess a particular genetic phenotype, such as expression of gonadotropin-releasing hormone (16). Both of these techniques have allowed examination of the physiological properties of neurons in vitro that possess presumed anatomical or functional correlates in the intact animal.We now report a neuron-labeling...

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Section: Discussionmentioning

confidence: 95%

mentioning

confidence: 99%

Pseudorabies virus expressing enhanced green fluorescent protein: A tool for in vitro electrophysiological analysis of transsynaptically labeled neurons in identified central nervous system circuits

Smith

Banfield

Smeraski

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

212

205

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“…Particular attention has been paid to the potential for mislabeling of neuronal circuits after intracranial injection of PRV. Direct PRV injection into brain ventricles, cerebral cavities filled with cerebrospinal fluid, showed that the neurons and the ependymal cells lining the ventricle and the caudal raphe could indeed be infected (74). Immunostaining for viral antigens shows that PRV can infect astrocytes and brain macrophages surrounding infected regions of the central nervous system.…”

Section: Containment Of Neuronal Infection By Cytoarchitecture and Nomentioning

confidence: 99%

“…When injected directly into brain tissue, PRV virions diffuse very little, producing a focal infection site. PRV could also infect neurons via fibers of passage, axons that traverse but do not synapse on cells at the injection site (74,189). Though the potential for leakage into the cerebrospinal fluid exists, PRV performs well as a tracer following intracranial injection (62).…”

Section: Containment Of Neuronal Infection By Cytoarchitecture and Nomentioning

confidence: 99%

Molecular Biology of Pseudorabies Virus: Impact on Neurovirology and Veterinary Medicine

Pomeranz

Reynolds

Hengartner

2005

Microbiol Mol Biol Rev

724

657

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Pseudorabies virus (PRV) is a herpesvirus of swine, a member of the Alphaherpesvirinae subfamily, and the etiological agent of Aujeszky's disease. This review describes the contributions of PRV research to herpesvirus biology, neurobiology, and viral pathogenesis by focusing on (i) the molecular biology of PRV, (ii) model systems to study PRV pathogenesis and neurovirulence, (iii) PRV transsynaptic tracing of neuronal circuits, and (iv) veterinary aspects of pseudorabies disease. The structure of the enveloped infectious particle, the content of the viral DNA genome, and a step-by-step overview of the viral replication cycle are presented. PRV infection is initiated by binding to cellular receptors to allow penetration into the cell. After reaching the nucleus, the viral genome directs a regulated gene expression cascade that culminates with viral DNA replication and production of new virion constituents. Finally, progeny virions self-assemble and exit the host cells. Animal models and neuronal culture systems developed for the study of PRV pathogenesis and neurovirulence are discussed. PRV serves as a self-perpetuating transsynaptic tracer of neuronal circuitry, and we detail the original studies of PRV circuitry mapping, the biology underlying this application, and the development of the next generation of tracer viruses. The basic veterinary aspects of pseudorabies management and disease in swine are discussed. PRV infection progresses from acute infection of the respiratory epithelium to latent infection in the peripheral nervous system. Sporadic reactivation from latency can transmit PRV to new hosts. The successful management of PRV disease has relied on vaccination, prevention, and testing

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“…Findings made in vivo (25,26,29,32,33,40,46,47) and in vitro (22,31) indicate that herpes viruses may be transferred transneurally in the retrograde direction from infected peripheral neuronal cell bodies and dendrites to presynaptic terminals on their surface and then retrogradely from these terminals to their parent cell bodies in the CNS. In particular, a strain of pseudorabies virus, PRVBartha, relies on its ability to infect chains of hierarchically connected neurons via the specific transsynaptic passage of progeny virus rather than infection by lytic release into the extracellular space and thus has been used successfully as a self-amplifying neural tracer after peripheral application or direct injection into brain parenchyma (6,7,27). Thus, viral entry into the sciatic nerves of the peripheral nervous system was one important pathway in the present study, and blocking entry from the inoculated tissues into the peripheral nerves using a specific antibody might have caused the decrease in death and neurological signs in the immunized mice.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of Intracerebral Immunization against Pseudorabies Virus in Mice

Shin

Sakoda

Kim

et al. 2006

Microbiology and Immunology

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Abstract:To evaluate the efficacy of intracerebral (IC) immunization, mice were immunized with formalininactivated pseudorabies virus (PRV) by either subcutaneous (SC) or IC injection, and then 10 6 plaqueforming units of PRV were introduced into the hindleg of the immunized or non-immunized mice by intramuscular injection. The antibody titer in serum was elevated and boosted by additional immunization via both the SC and IC routes, but was higher after IC immunization. Intracerebrally immunized mice were completely protected from mortality and neurological signs, whereas all the non-immunized and 80% of the subcutaneously immunized mice died after developing neurological signs. In mouse models, IC immunization is more effective at inducing a protective immune response against the transneural spread of PRV than SC immunization.

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Characterization of transsynaptic tracing with central application of pseudorabies virus

Cited by 56 publications

References 32 publications

Pseudorabies virus expressing enhanced green fluorescent protein: A tool for in vitro electrophysiological analysis of transsynaptically labeled neurons in identified central nervous system circuits

Pseudorabies virus expressing enhanced green fluorescent protein: A tool for in vitro electrophysiological analysis of transsynaptically labeled neurons in identified central nervous system circuits

Molecular Biology of Pseudorabies Virus: Impact on Neurovirology and Veterinary Medicine

Efficacy of Intracerebral Immunization against Pseudorabies Virus in Mice

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