Author(s): Sousa J?nior, Ivanildo P ; Carvalho, Carlos A. M ; Mendes, Ygara S ; Weissmuller, Gilberto ; Oliveira, Andr?a C ; Gomes, Andre M. O
Date: 2018
Origin: Oasisbr
Subject(s): Alphavirus; Alphavirus / qu?mica; Alphavirus / metabolismo; Lipossomos / qu?mica; Prote?nas Virais de Fus?o; Prote?nas Virais de Fus?o / qu?mica
This work was supported by an international grant from International Centre for Genetic Engineering and Biotechnology (ICGEB) and by Brazilian grants from Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (CAPES), Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico (CNPq), Funda??o Carlos Chagas Filho de Amparo ? Pesquisa do Estado do Rio de Janeiro (FAPERJ), Programa de Apoio ao Desenvolvimento Cient?fi?co e Tecnolo?gico (PADCT), and Programa de Apoio a Nucleos de Excel?ncia (PRONEX).
Universidade Federal do Rio de Janeiro. Instituto de Bioqu?mica M?dica Leopoldo de Meis. Centro de Ci?ncias da Sa?de. Rio de Janeiro, RJ, Brazil / Funda??o Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brazil.
Funda??o Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brazil / Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil.
Funda??o Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brazil / Funda??o Oswaldo Cruz. Instituto de Tecnologia em Imunobiolo?gicos. Rio de Janeiro, RJ, Brazil.
Universidade Federal do Rio de Janeiro. Instituto de Biof?sica Carlos Chagas Filho. Centro de Ci?ncias da Sa?de. Rio de Janeiro, RJ, Brazil.
Universidade Federal do Rio de Janeiro. Instituto de Bioqu?mica M?dica Leopoldo de Meis. Centro de Ci?ncias da Sa?de. Rio de Janeiro, RJ, Brazil.
Universidade Federal do Rio de Janeiro. Instituto de Bioqu?mica M?dica Leopoldo de Meis. Centro de Ci?ncias da Sa?de. Rio de Janeiro, RJ, Brazil.
Alphaviruses are enveloped arboviruses mainly proposed to infect host cells by receptor-mediated endocytosis followed by fusion between the viral envelope and the endosomal membrane. The fusion reaction is triggered by low pH and requires the presence of both cholesterol and sphingolipids in the target membrane, suggesting the involvement of lipid rafts in the cell entry mechanism. In this study, we show for the first time the interaction of an enveloped virus with membrane microdomains isolated from living cells. Using Mayaro virus (MAYV), a New World alphavirus, we verified that virus fusion to these domains occurred to a significant extent upon acidification, although its kinetics was quite slow when compared to that of fusion with artificial liposomes demonstrated in a previous work. Surprisingly, when virus was previously exposed to acidic pH, a condition previously shown to inhibit alphavirus binding and fusion to target membranes as well as infectivity, and then reneutralized, its ability to fuse with membrane microdomains at low pH was retained. Interestingly, this observation correlated with a partial reversion of low pH-induced conformational changes in viral proteins and retention of virus infectivity upon reneutralization. Our results suggest that MAYV entry into host cells could alternatively involve internalization via lipid rafts and that the conformational changes triggered by low pH in the viral spike proteins during the entry process are partially reversible.
