Temporal expression of Zika virus genes from strains of African and Brazilian and mapping of the gene expression in permissive, semi- permissive and non- permissive systems

Abstract

The Zika virus was first described in 1947 in the Zika forest of Uganda, Africa. This virus was isolated from a macaque and inoculated in a mouse brain at the time, resulting in the detection of a filterable infectious agent, later called Zika virus (ZIKV). Then the same virus was isolated from species of Aedes africanus mosquitoes, a mosquito that keeps close evolutionary relationship with the Aedes aegypti species, which is very common in Brazil. The Zika virus is a member of the Flaviviridae family of arboviruses and until recently was a virus with little relevance and expression worldwide, confined to a narrow ecological niche and also limited to a few animal hosts and restricted to the equatorial belt of Africa and Asia. The current epidemic caused by this arbovirus called the world's attention to Brazil. At the moment there are reports of infection occurring in South and Central America and the Caribbean, with ramifications for the United States, Europe and also hitting China recently. Previous work from our group have shown that the genome of the virus is closely related to Dengue virus and the preliminary results presented in this project and our recent work revealed an important evolutionary adaptation of the virus related to the use of codons of the host for efficient expression of its viral proteins, linear and structural epitopes are also shared with Dengue viruses. However, when comparing the African and Brazilian strain produced in cells permissive and semi-permissive, we will be able to measure those differences, such as the low and high level of expression of certain viral genes. In order to do this we aim to (i) identify qualitative and quantitative differences in messenger RNA (mRNA) resulting from infection Zika African and Brazilian strain in different cell substracts; (ii) analyze in silico the possible changes found in standard Zika mRNA expression for both strains studied, which will allow to observe targets for future gene silencing; (iii) Map in silico the differentially expressed ORFs both for the host and the viruses; (iv) analyze the possible changes and propose the network of gene expression involved in the interaction of the strains studied and finally (IIV) investigate whether the regulation of gene expression in Zika passed through different hosts is congruent with other RNA viruses. Understanding how these processes work together given the proposed experimental design herein will be crucial in understanding the networks that are disturbed in the course of this infection. (AU)