Varicella Zoster Virus Induces Nuclear Translocation of the Neurokinin-1 Receptor, Promoting Lamellipodia Formation and Viral Spread in Spinal Astrocytes.
J Infect Dis
; 218(8): 1324-1335, 2018 09 08.
Article
em En
| MEDLINE
| ID: mdl-29788447
ABSTRACT
Background:
Varicella zoster virus (VZV) can present as a myelopathy with spinal astrocyte infection. Recent studies support a role for the neurokinin-1 receptor (NK-1R) in virus infections, as well as for cytoskeletal alterations that may promote viral spread. Thus, we examined the role of NK-1R in VZV-infected primary human spinal astrocytes (HA-sps) to shed light on the pathogenesis of VZV myelopathy.Methods:
Mock- and VZV-infected HA-sps were examined for substance P (subP) production, NK-1R localization, morphological changes, and viral spread in the presence or absence of the NK-1R antagonists aprepitant and rolapitant.Results:
VZV infection of HA-sps induced nuclear localization of full-length and truncated NK-1R in the absence of the endogenous ligand, subP, and was associated with extensive lamellipodia formation and viral spread that was inhibited by NK-1R antagonists.Conclusions:
We have identified a novel, subP-independent, proviral function of nuclear NK-1R associated with lamellipodia formation and viral spread that is distinct from subP-induced NK-1R cell membrane/cytoplasmic localization without lamellipodia formation. These results suggest that binding of a putative viral ligand to NK-1R produces a dramatically different NK-1R downstream effect than binding of subP. Finally, the NK-1R antagonists aprepitant and rolapitant provide promising alternatives to nucleoside analogs in treating VZV infections, including myelopathy.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pseudópodes
/
Astrócitos
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Receptores da Neurocinina-1
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Herpesvirus Humano 3
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Transporte Ativo do Núcleo Celular
Limite:
Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article