Abstract
Virus infections often lead to formation of aggregates and aggresomes in host cells. In this study, production of aggregates and aggresomes by the highly expressed protein polyhedrin of Bombyx mori nucleopolyhedrovirus (BmNPV) at 24 h postinfection (p.i.) was detected with a fluorescent molecular dye, and verified by colocalization of polyhedrin with aggresomal markers, GFP-250 and γ−tubulin. Polyhedrin aggregates showed hallmark characteristics of aggresomes: formation was microtubule-dependent; they colocalized with heat shock cognates/proteins of the 70-kDa family (HSC/HSP70s), ubiquitinated proteins and recruited the mitochondria. Aggregated polyhedrin protein gradually gained its active conformation accompanying progress of BmNPV infection. At 48 h p.i. recovered polyhedrin bound directly to Bombyx mori microtubule-associated protein 1-light chain 3 (BmLC3), an autophagosome marker, and was colocalized with BmLC3 to the isolation membrane of autophagosome, implying the involvement of polyhedrin in cellular autophagy. Inhibition of autophagy by 3-methyladenine (3-MA) dramatically resulted in decrease of polyhedrin expression and polyhedra particle production. These observations suggested that highly expressed polyhedrin forms aggregate to get involved in cellular autophagy then play an important role in polyhedra production.
Highlights
A hallmark of many neurodegenerative disorders, such as Alzheimer’s disease, Huntington’s disease, Parkinson’s disease and oculopharyngeal muscular dystrophy, is the presence of misfolded protein aggregates[1]
Infection of herpes simplex virus led to the formation of aggresomes and some tegument proteins such as UL46 and VP16 were targeted to aggresomes[11,12]
Once produced in the cytoplasm, aggregated proteins are refolded by some molecular chaperones and remodeling factors to obtain their active conformations thereby reducing the likelihood of protein aggregation[4]
Summary
A hallmark of many neurodegenerative disorders, such as Alzheimer’s disease, Huntington’s disease, Parkinson’s disease and oculopharyngeal muscular dystrophy, is the presence of misfolded protein aggregates[1]. Aggregates may form because of genetic mutation, errors in transcription, mRNA processing or translation. They can be produced in response to some environmental factors, such as hyperthermia, exposure to reactive oxygen species and chemical treatment[2,3]. Cells remove toxic protein aggregates using a variety of homestatic mechanisms, such as refolding by some protein chaperones and remodeling factors to obtain their active conformations[4], and degradation by the ubiquitin-proteasome pathway and chaperone-mediated autophagy[5]. In adenovirus-infected cells, expression of either E4 11k or E1b 55k, can individually induce aggresome formation, and both relocate www.nature.com/scientificreports/. Infection of herpes simplex virus led to the formation of aggresomes and some tegument proteins such as UL46 and VP16 were targeted to aggresomes[11,12]
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