Innervation of the Heart and Its Central Medullary Origin Defined by Viral Tracing

Standish, A.; Enquist, Lynn W.; Schwaber, James S.

doi:10.1126/science.8284675

Cited by 161 publications

(95 citation statements)

References 14 publications

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“…By contrast, gI and gE mutant viruses replicate well in the eye but do not spread to secondorder CNS neurons in a major subset of visual centers such as the superior colliculus and the dorsal lateral geniculate nucleus (dLGN). A similar inability to infect a subset of cardiac neurons in the rat brain stem has been reported following inoculation of gE mutants into the heart (26,27). Similar defects in directional spread of infection have been noted after infection of mice by PRV gE and gI mutants (1).…”

mentioning

confidence: 57%

Pseudorabies Virus Membrane Proteins gI and gE Facilitate Anterograde Spread of Infection in Projection- Specific Neurons in the Rat

Husak

Kuo

Enquist

2000

J Virol

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The membrane proteins gI and gE of Pseudorabies virus (PRV) are required for viral invasion and spread through some neural pathways of the rodent central nervous system. Following infection of the rat retina with wild-type PRV, virus replicates in retinal ganglion neurons and anterogradely spreads to infect all visual centers in the brain. By contrast, gI and gE null mutants do not infect a specific subset of the visual centers, e.g., the superior colliculus and the dorsal lateral geniculate nucleus. In previous experiments, we suggested that the defect was not due to inability to infect projection-specific retinal ganglion cells, because mixed infection of a gE deletion mutant and a gI deletion mutant restored the wild-type phenotype (i.e., genetic complementation occurred). In the present study, we provide direct evidence that gE and gI function to promote the spread of infection after entry into primary neurons. We used stereotaxic central nervous system injection of a fluorescent retrograde tracer into the superior colliculus and subsequent inoculation of a PRV gI-gE double null mutant into the eye of the same animal to demonstrate that viral antigen and fluorescent tracer colocalize in retinal ganglion cells. Furthermore, we demonstrate that direct injection of a PRV gI-gE double null mutant into the superior colliculus resulted in robust infection followed by retrograde transport to the eye and replication in retinal ganglion neuron cell bodies. These experiments provide additional proof that the retinal ganglion cells projecting to the superior colliculus are susceptible and permissive to gE and gI mutant viruses. Our studies confirm that gI and gE specifically facilitate anterograde spread of infection by affecting intracellular processes in the primary infected neuron such as anterograde transport in axons or egress from axon terminals.Alphaherpesviruses, like Herpes simplex virus types 1 and 2 (HSV-1 and HSV-2), Varicella-zoster virus, and Pseudorabies virus (PRV), exhibit a predilection to infect neurons in the central nervous system (CNS) and peripheral nervous system (PNS) of an animal host (9a). During natural infections, virus replicates in nonneuronal cells and then undergoes retrograde spread of virus into afferent (e.g., sensory) or efferent (e.g., motor) nerve fibers innervating the infected tissue. Typically, this viral infection is limited to the PNS, where a latent infection is established in neurons directly innervating the peripheral site. Reactivation from latency is associated with virus replication in the primary neuron followed by anterograde transport of newly synthesized virus particles from the neuronal cell body back to the innervated tissue. Although less frequent, virus may also spread from the PNS to the CNS following primary infection or reactivation; this often has fatal consequences for the host. Hence, alphaherpesviruses are likely to encode mechanisms that facilitate travel in either direction within a neural circuit and thus may regulate the choice of direction at differe...

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mentioning

confidence: 57%

Pseudorabies Virus Membrane Proteins gI and gE Facilitate Anterograde Spread of Infection in Projection- Specific Neurons in the Rat

Husak

Kuo

Enquist

2000

J Virol

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“…Multiple ganglia innervate the ventricular myocardium, and it is possible that if neural activity had been recorded from the dorsal ventricular fat pad, abnormal responses to right VNS may have been noted. Given the infarct location, it's also possible that afferent signaling to the brainstem -especially the left nucleus tractus solitarius, which provides input to the left nucleus ambiguus and left dorsal motor nucleus of the vagus -is altered and leads to a reduction of parasympathetic drive through the left vagal trunk (25)(26)(27). However, both vagal trunks are needed to maintain normal parasympathetic tone, and transection of one trunk can have significant electrophysiological consequences in porcine and canine hearts (28,29).…”

Section: Discussionmentioning

confidence: 99%

Parasympathetic dysfunction and antiarrhythmic effect of vagal nerve stimulation following myocardial infarction

Vaseghi¹,

Salavatian²,

Rajendran³

et al. 2017

JCI Insight

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“…The nA contains pharyngeal and laryngeal motoneurons that govern the upper airway valve as well as motoneurons innervating the esophagus, all of which are involved in respiratory and swallowing behaviors (Bieger and Hopkins, 1987;Standish et al, 1994). The survival requirements of nA motoneurons have not been widely studied.…”

Section: Tshz3 Mutation Impairs Survival Of Motoneurons Of the Nucleumentioning

confidence: 99%

Teashirt 3 Regulates Development of Neurons Involved in Both Respiratory Rhythm and Airflow Control

Caubit¹,

Thoby‐Brisson²,

Voituron³

et al. 2010

Journal of Neuroscience

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Neonatal breathing in mammals involves multiple neuronal circuits, but its genetic basis remains unclear. Mice deficient for the zinc finger protein Teashirt 3 (TSHZ3) fail to breathe and die at birth. Tshz3 is expressed in multiple areas of the brainstem involved in respiration, including the pre-Bötzinger complex (preBötC), the embryonic parafacial respiratory group (e-pF), and cranial motoneurons that control the upper airways. Tshz3 inactivation led to pronounced cell death of motoneurons in the nucleus ambiguus and induced strong alterations of rhythmogenesis in the e-pF oscillator. In contrast, the preBötC oscillator appeared to be unaffected. These deficits result in impaired upper airway function, abnormal central respiratory rhythm generation, and altered responses to pH changes. Thus, a single gene, Tshz3, controls the development of diverse components of the circuitry required for breathing.

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Innervation of the Heart and Its Central Medullary Origin Defined by Viral Tracing

Cited by 161 publications

References 14 publications

Pseudorabies Virus Membrane Proteins gI and gE Facilitate Anterograde Spread of Infection in Projection- Specific Neurons in the Rat

Pseudorabies Virus Membrane Proteins gI and gE Facilitate Anterograde Spread of Infection in Projection- Specific Neurons in the Rat

Parasympathetic dysfunction and antiarrhythmic effect of vagal nerve stimulation following myocardial infarction

Teashirt 3 Regulates Development of Neurons Involved in Both Respiratory Rhythm and Airflow Control

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