About: Coronavirus Gene 7 Counteracts Host Defenses and Modulates Virus Virulence

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An Entity of Type : schema:ScholarlyArticle, within Data Space : wasabi.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Coronavirus Gene 7 Counteracts Host Defenses and Modulates Virus Virulence
Creator	Plana, J Sola, I Alberca, B Becares, M Cruz, Jlg
Source	Medline; PMC
abstract	Transmissible gastroenteritis virus (TGEV) genome contains three accessory genes: 3a, 3b and 7. Gene 7 is only present in members of coronavirus genus a1, and encodes a hydrophobic protein of 78 aa. To study gene 7 function, a recombinant TGEV virus lacking gene 7 was engineered (rTGEV-Δ7). Both the mutant and the parental (rTGEV-wt) viruses showed the same growth and viral RNA accumulation kinetics in tissue cultures. Nevertheless, cells infected with rTGEV-Δ7 virus showed an increased cytopathic effect caused by an enhanced apoptosis mediated by caspase activation. Macromolecular synthesis analysis showed that rTGEV-Δ7 virus infection led to host translational shut-off and increased cellular RNA degradation compared with rTGEV-wt infection. An increase of eukaryotic translation initiation factor 2 (eIF2α) phosphorylation and an enhanced nuclease, most likely RNase L, activity were observed in rTGEV-Δ7 virus infected cells. These results suggested that the removal of gene 7 promoted an intensified dsRNA-activated host antiviral response. In protein 7 a conserved sequence motif that potentially mediates binding to protein phosphatase 1 catalytic subunit (PP1c), a key regulator of the cell antiviral defenses, was identified. We postulated that TGEV protein 7 may counteract host antiviral response by its association with PP1c. In fact, pull-down assays demonstrated the interaction between TGEV protein 7, but not a protein 7 mutant lacking PP1c binding motif, with PP1. Moreover, the interaction between protein 7 and PP1 was required, during the infection, for eIF2α dephosphorylation and inhibition of cell RNA degradation. Inoculation of newborn piglets with rTGEV-Δ7 and rTGEV-wt viruses showed that rTGEV-Δ7 virus presented accelerated growth kinetics and pathology compared with the parental virus. Overall, the results indicated that gene 7 counteracted host cell defenses, and modified TGEV persistence increasing TGEV survival. Therefore, the acquisition of gene 7 by the TGEV genome most likely has provided a selective advantage to the virus.
has issue date	2011-06-09(xsd:dateTime)
bibo:doi	10.1371/journal.ppat.1002090
bibo:pmid	21695242
has license	cc-by
sha1sum (hex)	ebe8d3845bdfbc11f865667d68399c4862551d30
schema:url	https://doi.org/10.1371/journal.ppat.1002090
resource representing a document's title	Coronavirus Gene 7 Counteracts Host Defenses and Modulates Virus Virulence
has PubMed Central identifier	PMC3111541
has PubMed identifier	21695242
schema:publication	PLoS Pathog
resource representing a document's body	covid:ebe8d3845bdfbc11f865667d68399c4862551d30#body_text
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