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A herpesvirus encoded deubiquitinase is a novel neuroinvasive determinant.

Lee JI, Sollars PJ, Baver SB, Pickard GE, Leelawong M, Smith GA - PLoS Pathog. (2009)

Bottom Line: The neuroinvasive property of several alpha-herpesviruses underlies an uncommon infectious process that includes the establishment of life-long latent infections in sensory neurons of the peripheral nervous system.Whether initial entry into the nervous system from peripheral tissues also requires specialized viral functions is not known.These findings indicate that the deubiquitinase contributes to neurovirulence by participating in a previously unrecognized initial step in neuroinvasion.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.

ABSTRACT
The neuroinvasive property of several alpha-herpesviruses underlies an uncommon infectious process that includes the establishment of life-long latent infections in sensory neurons of the peripheral nervous system. Several herpesvirus proteins are required for replication and dissemination within the nervous system, indicating that exploiting the nervous system as a niche for productive infection requires a specialized set of functions encoded by the virus. Whether initial entry into the nervous system from peripheral tissues also requires specialized viral functions is not known. Here we show that a conserved deubiquitinase domain embedded within a pseudorabies virus structural protein, pUL36, is essential for initial neural invasion, but is subsequently dispensable for transmission within and between neurons of the mammalian nervous system. These findings indicate that the deubiquitinase contributes to neurovirulence by participating in a previously unrecognized initial step in neuroinvasion.

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Related in: MedlinePlus

Viral transport dynamics in axons of cultured primary neurons.(A) Representative example of retrograde transport of an individual capsid in a dorsal root sensory axon after infection with the C26A virus, shown as a time-lapse montage. All frames are 1.68×10.8 µm. (B) Retrograde transport efficiency measured as frame-by-frame velocities of individual capsid particles in axons (as documented in panel A). (C) Anterograde transport efficiency measured by accumulation of newly replicated capsids in axons.
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ppat-1000387-g002: Viral transport dynamics in axons of cultured primary neurons.(A) Representative example of retrograde transport of an individual capsid in a dorsal root sensory axon after infection with the C26A virus, shown as a time-lapse montage. All frames are 1.68×10.8 µm. (B) Retrograde transport efficiency measured as frame-by-frame velocities of individual capsid particles in axons (as documented in panel A). (C) Anterograde transport efficiency measured by accumulation of newly replicated capsids in axons.

Mentions: To determine if the C26A virus was capable of intracellular transport in both the retrograde and anterograde directions, we examined axonal transport in cultured dorsal root sensory neurons by tracking red-fluorescence emissions from capsid particles by time-lapse microscopy. In these assays, the C26A virus behaved similarly to the wild-type virus, having only small decreases in axon transport during both stages of infection (Figure 2). These findings demonstrate that intracellular transport of the C26A virus was intact, and suggests the defect observed after intravitreal injection was likely due to a change in intercellular viral spread in animals. While these results did not immediately explain the defect observed in spread through retrograde sympathetic and parasympathetic circuits following intravitreal inoculation (i.e. to the EW and PVN), they were consistent with the one instance of C26A virus spread to the oculomotor region of the midbrain.


A herpesvirus encoded deubiquitinase is a novel neuroinvasive determinant.

Lee JI, Sollars PJ, Baver SB, Pickard GE, Leelawong M, Smith GA - PLoS Pathog. (2009)

Viral transport dynamics in axons of cultured primary neurons.(A) Representative example of retrograde transport of an individual capsid in a dorsal root sensory axon after infection with the C26A virus, shown as a time-lapse montage. All frames are 1.68×10.8 µm. (B) Retrograde transport efficiency measured as frame-by-frame velocities of individual capsid particles in axons (as documented in panel A). (C) Anterograde transport efficiency measured by accumulation of newly replicated capsids in axons.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2663050&req=5

ppat-1000387-g002: Viral transport dynamics in axons of cultured primary neurons.(A) Representative example of retrograde transport of an individual capsid in a dorsal root sensory axon after infection with the C26A virus, shown as a time-lapse montage. All frames are 1.68×10.8 µm. (B) Retrograde transport efficiency measured as frame-by-frame velocities of individual capsid particles in axons (as documented in panel A). (C) Anterograde transport efficiency measured by accumulation of newly replicated capsids in axons.
Mentions: To determine if the C26A virus was capable of intracellular transport in both the retrograde and anterograde directions, we examined axonal transport in cultured dorsal root sensory neurons by tracking red-fluorescence emissions from capsid particles by time-lapse microscopy. In these assays, the C26A virus behaved similarly to the wild-type virus, having only small decreases in axon transport during both stages of infection (Figure 2). These findings demonstrate that intracellular transport of the C26A virus was intact, and suggests the defect observed after intravitreal injection was likely due to a change in intercellular viral spread in animals. While these results did not immediately explain the defect observed in spread through retrograde sympathetic and parasympathetic circuits following intravitreal inoculation (i.e. to the EW and PVN), they were consistent with the one instance of C26A virus spread to the oculomotor region of the midbrain.

Bottom Line: The neuroinvasive property of several alpha-herpesviruses underlies an uncommon infectious process that includes the establishment of life-long latent infections in sensory neurons of the peripheral nervous system.Whether initial entry into the nervous system from peripheral tissues also requires specialized viral functions is not known.These findings indicate that the deubiquitinase contributes to neurovirulence by participating in a previously unrecognized initial step in neuroinvasion.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.

ABSTRACT
The neuroinvasive property of several alpha-herpesviruses underlies an uncommon infectious process that includes the establishment of life-long latent infections in sensory neurons of the peripheral nervous system. Several herpesvirus proteins are required for replication and dissemination within the nervous system, indicating that exploiting the nervous system as a niche for productive infection requires a specialized set of functions encoded by the virus. Whether initial entry into the nervous system from peripheral tissues also requires specialized viral functions is not known. Here we show that a conserved deubiquitinase domain embedded within a pseudorabies virus structural protein, pUL36, is essential for initial neural invasion, but is subsequently dispensable for transmission within and between neurons of the mammalian nervous system. These findings indicate that the deubiquitinase contributes to neurovirulence by participating in a previously unrecognized initial step in neuroinvasion.

Show MeSH
Related in: MedlinePlus