Proteomics

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The axonal sorting activity of pseudorabies virus Us9 protein depends on the state of neuronal maturation The axonal sorting activity of pseudorabies virus Us9 protein depends on the state of neuronal maturation


ABSTRACT: Alpha-herpesviruses establish a life-long infection in the nervous system of the affected host; while this infection is restricted to peripheral neurons in a heathy host, it can spread within the neuronal circuitry in compromised individuals leading to adverse health consequences. Pseudorabies virus (PRV) an alpha-herpesvirus, requires the viral protein Us9 for sorting virus particles into axons. It does so by mediating an interaction of virus particles with neuronal transport machinery. Us9-mediated axonal sorting also depends on the state of neuronal maturation as the proteome composition changes with neuronal development of dendrites and axons. Immature superior cervical ganglia (SCGs) have rudimentary neurites that lack markers of mature dendrites or axons. Immature SCGs can be infected by PRV, but show markedly reduced Us9-dependent sorting into neurites. Mature SCGs abundantly express a variety of proteins characteristic of vesicle-transport machinery. Proteomics studies identified several novel Us9-associated neuronal proteins with potential roles in the regulation of axonal sorting and subsequent anterograde spread of virus particles in axons. For example, we found that SMPD4/n-sMase3, a sphingomyelinase abundant in lipid-rafts, associates with Us9 and is a negative regulator of axonal mediated spread of PRV, a potential novel antiviral function.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Rattus Norvegicus (rat)

SUBMITTER: Joel Federspiel  

LAB HEAD: Ileana Cristea

PROVIDER: PXD017822 | Pride | 2021-01-04

REPOSITORIES: Pride

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The axonal sorting activity of pseudorabies virus Us9 protein depends on the state of neuronal maturation.

Tanneti Nikhila S NS   Federspiel Joel D JD   Cristea Ileana M IM   Enquist Lynn W LW  

PLoS pathogens 20201228 12


Alpha-herpesviruses establish a life-long infection in the nervous system of the affected host; while this infection is restricted to peripheral neurons in a healthy host, the reactivated virus can spread within the neuronal circuitry, such as to the brain, in compromised individuals and lead to adverse health outcomes. Pseudorabies virus (PRV), an alpha-herpesvirus, requires the viral protein Us9 to sort virus particles into axons and facilitate neuronal spread. Us9 sorts virus particles by med  ...[more]

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