Dengue virus-1 NS5 genetic variant associated with a severe clinical infection: Possible reduction of the innate immune response by inhibition of interferon type 1 and the Janus kinase-signal transducer and activator of transcription signaling pathway.

Abstract	Dengue virus (DENV) is currently considered as one of the most important mosquito-borne viral pathogens affecting humans. Genetic variations in viruses are likely to be a condition for more effective evasion of the immune system and resulting in severe clinical consequences. The DENV‑1 NS5 gene was sequenced to establish whether during an epidemic burst there were genetic variations of the virus and whether any variant was associated (through a case‑control design) with severe clinical behavior. A total of 31 patients positive for DENV‑1 were enrolled. Among the nucleotide differences between the sequences, only two generated amino acid changes. The variants 124Met/166Ser (amino acid positions according to the report GenBank AJL35015.1), were associated with a severe clinical course of the disease. Via in silico tests, it was identified that the variations generate changes in the protein probably affecting the function of type‑1 interferon, either at the level of its receptor or by interfering with the Janus kinase‑signal transducer and activator of transcription signaling pathway.
Authors	Iván Delgado-Enciso, Uriel A López-Lemus, Jose A Valcarcel-Gamiño, Iram P Rodriguez-Sanchez, Salvador Valle-Reyes, Margarita L Martinez-Fierro, Valery Melnikov, José Guzmán-Esquivel, Felipe Vaca-Paniagua, Laura L Valdez-Velazquez, Luz M Baltazar-Rodriguez, Alejandro D Soriano-Hernandez, Brenda Paz-Michel, Francisco Espinoza-Gómez
Journal	International journal of molecular medicine (Int J Mol Med) Vol. 41 Issue 4 Pg. 2263-2269 (Apr 2018) ISSN: 1791-244X [Electronic] Greece
PMID	29344662 (Publication Type: Journal Article)
Chemical References	Interferon Type I NS5 protein, dengue virus STAT Transcription Factors Viral Nonstructural Proteins Janus Kinase 1 Janus Kinases
Topics	Adolescent Adult Aged Aged, 80 and over Child Dengue (immunology, virology) Dengue Virus (genetics, immunology) Female Genetic Variation Humans Immunity, Innate Interferon Type I (immunology) Janus Kinase 1 (immunology) Janus Kinases (immunology) Male Middle Aged Molecular Docking Simulation Point Mutation STAT Transcription Factors (immunology) Signal Transduction Viral Nonstructural Proteins (genetics, immunology) Young Adult

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