ABSTRACT
Resumen Introducción. El virus del Zika (ZIKV) es un flavivirus con envoltura, transmitido a los seres humanos principalmente por el vector Aedes aegypti. La infección por ZIKV se ha asociado con un gran neurotropismo y con efectos neuropáticos, como el síndrome de Guillain-Barré en el adulto y la microcefalia fetal y posnatal, así como con un síndrome de infección congénita similar al producido por el virus de la rubéola (RV). Objetivo. Comparar las estructuras moleculares de la proteína de envoltura E del virus del Zika (E-ZIKV) y de la E1 del virus de la rubéola (E1-RV), y plantear posibles implicaciones en el neurotropismo y en las alteraciones del sistema nervioso asociadas con el ZIKV. Materiales y métodos. La secuencia de aminoácidos de la proteína E-ZIKV (PDB: 5iZ7) se alineó con la de la glucopreteína E1 del virus de la rubéola (PDB: 4ADG). Los elementos de la estructura secundaria se determinaron usando los programas Vector NTI Advance®, DSSP y POSA, así como herramientas de gestión de datos (AlignX®). Uno de los criterios principales de comparación y alineación fue la asignación de residuos estructuralmente equivalentes, con más de 70 % de identidad. Resultados. La organización estructural de la proteína E-ZIKV (PDB: 5iZ7) fue similar a la de E1-RV (PDB: 4ADG) (70 a 80 % de identidad), y se observó una correspondencia con la estructura definida para las glucoproteínas de fusión de membrana de clase II de los virus con envoltura. E-ZIKV y E1-RV exhibieron elementos estructurales de fusión muy conservados en la región distal del dominio II, asociados con la unión a los receptores celulares de entrada del virus de la rubéola (glucoproteína de mielina del oligodendrocito, Myelin Oligodendrocyte Glycoprotein, MOG), y con los receptores celulares Axl del ZIKV y de otros flavivirus. Conclusión. La comparación de las proteínas E-ZIKV y E1-RV es un paso necesario hacia la definición de otros factores moleculares determinantes del neurotropismo y la patogenia del ZIKV, el cual puede contribuir a generar estrategias de diagnóstico, prevención y tratamiento de las complicaciones neurológicas inducidas por el ZIKV.
Abstract Introduction: Zika virus (ZIKV) is an enveloped flavivirus transmitted to humans mainly by Aedes aegypti. ZIKV infection has been associated with high neurotropism and neuropathic effects such as the Guillain-Barré syndrome in adults, and fetal and postnatal microcephaly and the congenital Zika virus syndrome similar to that produced by rubella virus (VR). Objective: To compare Zika virus membrane protein E (E-ZIKV) and rubella virus membrane protein E1 (E1-RV), and to propose possible implications for neurotropism and nervous system disorders associated with ZIKV infections. Materials and methods: The amino acid sequence of E-ZIKV protein (PDB: 5iZ7) was aligned to that of rubella virus glycoprotein E1 (PDB: 4ADG). The secondary structure elements were determined using the programs Vector NTI Advance®, DSSP, and POSA, and integrated data management tools (AlignX®). One of the main comparison and alignment criteria was the allocation of structurally equivalent residues with more than 70% identity. Results: E-ZIKV structural organization (PDB: 5iZ7) was similar to that of E1-RV (PDB: 4ADG) (70%-80% identity), and it was consistent with relevant structural features of viral membrane class II fusion glycoproteins. E-ZIKV and E1-RV exhibited highly conserved fusion structural elements at the distal region of domain II, which has been associated with the RV myelin oligodendrocyte glycoprotein and Axl cell receptors in ZIKV and other flaviviruses. Conclusion: The comparison of E-ZIKV and E1-RV proteins constitutes an essential step towards the definition of ZIKV neurotropism and pathogenesis molecular determinants, and for the adoption of diagnosis, prevention and treatment strategies against neurological complications induced by ZIKV infection.
Subject(s)
Humans , Viral Proteins/chemistry , Serine Endopeptidases/metabolism , Serine Endopeptidases/chemistry , Viral Envelope Proteins/metabolism , Zika Virus/chemistry , Measles virus/chemistry , Viral Proteins/physiology , Viral Proteins/genetics , Zika Virus/physiology , Zika Virus/pathogenicity , Measles virus/physiology , Measles virus/pathogenicity , Molecular BiologyABSTRACT
Objective To observe the effect of early intervention on the oligodendrocyte-myelin glycoprotein(OMgp) mRNA expression of brain injury neonatal rats caused by intrauterine infection.Methods 1.Twenty-eight Wistar pregnant rats were randomly divided into 2 groups:lipopolysaccharide(LPS)-treated group and saline control group.Pregnant rats were consecutively injected with LPS (450 ?g?kg-1) or saline on the 18th gestation age.After birth,the placentas were taken out and made HE staining to observe intrauterine infection.2.Thirty neonatal rats in the saline control group and 55 rats in the LPS-treated group were randomly selected which were divided into intervention group (n=25) and no-intervention group (n=25).The second post-natal day (P2) rats in intervention group were treated by early touch and enriched environment.The neonatal rats in the no-intervention group and saline control group were fed in a routine way.Five cases of P1 rats were selected respectively from the LPS-treated group and saline control group,and brain tissue pathological section was made to observe the condition of brain injury.3.Five cases of P1,P3,P7,P28 and P42 rats were selected from the saline control group,intervention group and no-intervention group to detect the OMgp mRNA expression levels by using the real time polymerase chain reaction me-thod.Results 1.There were a great number of neurophilic granulocytes in the placentas in the LPS-treated group.2.Brain tissue pathological of P1 in the saline control group had complete substantia alba structure,ordered disposition and lightly stained clear chromatospherite.While in the LPS-treated group, there existed brain tissue looseness,colloid cell aggregation and oligodendrocyte cytoreduction in the position of substantia alba,callositas and capsula interna.Intraventricular hemorrhage,substantia alba blood vessel dilatation and blood capillary angiorrhexis and hemorrhage could also be found.3.There was a higher increase in OMgp mRNA expressions of brain tissue in the LPS-treated group at P1,P3,P7,P28,P42 than those in the saline control group (Pa