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Master's Dissertation
DOI
https://doi.org/10.11606/D.42.2018.tde-05022018-105308
Document
Author
Full name
Tábata Dilenardi Dias
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2017
Supervisor
Committee
Ventura, Armando Morais (President)
Botosso, Viviane Fongaro
Monteiro, Hugo Pequeno
Pierulivo, Enrique Mario Boccardo
Title in Portuguese
Interação entre tropomiosina e as proteínas de matriz e fosfoproteína do vírus respiratório sincicial humano.
Keywords in Portuguese
Fosfoproteína
Interação célula-vírus
Matriz
Tropomiosina
Vírus respiratório sincicial humano
Abstract in Portuguese
O Vírus Respiratório Sincicial Humano (HRSV) causa doença respiratória principalmente em recém-nascidos e bebês. A infecção por HRSV exerce forte interferência sobre a localização de actina, fenômeno que propomos estar relacionado à interação de TPM com M e P, levando ao rearranjo dos microtúbulos. Os objetivos gerais do projeto são de analisar interações in vitro, em bactéria e em célula entre TPM com M e P. Os dados obtidos indicam que ocorre a interação in vitro entre M e TPM 3 mas não ocorre entre P e TPM 3. Os estudos realizados em célula indicam a interação de M e P com TPM 3. Com siRNA para TPM 3 os dados não foram conclusivos e para a super expressão de TPM 3 verificamos que ocorre inibição da replicação viral. Testamos uma droga que desacopla TPM 3 dos filamentos de actina e os resultados indicam inibição da replicação viral. Concluímos com esses dados que TPM 3 tem papel fundamental no ciclo replicativo do vírus e que sua interação com M tem potencial para ser explorada como alvo terapêutico no desenvolvimento de antivirais contra HRSV.
Title in English
Interaction between tropomyosin and the human respiratory syncytial virus proteins matrix and phosphoprotein.
Keywords in English
Human respiratory syncytial virus
Matrix
Phosphoprotein
Tropomyosin
Virus-cell interaction
Abstract in English
Human Respiratory Syncytial Virus (HRSV) causes respiratory disease in newborns and babies. The HRSV infection exerts strong interference on intracellular location of actin, a phenomenon that we propose to be connected to the interaction of TPM with M and P, leading to the rearrangement of microtubules. In this project we propose to analyze interactions in vitro, in bacteria and in cells between TPM and P or M. The obtained data indicate that an in vitro interaction between M and TPM occurs but does not occur between P and TPM. Cell studies indicate an interaction of M and P with TPM. With siRNA fot TPM 3 the data were not conclusive, and for overexpression of TPM 3 an inhibition of virus replication was shown. Also, in cell, we obtained results indicating that the use of a cytoskeletal destabilizing drug is affecting viral replication. These data indicate that Tropomyosin plays a key role in the virus cycle and therefore has the potential to be exploited as a therapeutic target in the development of antiviral drugs against HRSV.
 
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Release Date
2020-02-05
Publishing Date
2018-02-05
 
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