Transcriptomic analysis of Rhesus monkeys during acute infection by Zika Virus

Author(s)

Mariana Araújo Pereira

• Document type: Master's Dissertation
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Instituto de Matemática e Estatística (IME/SBI)
• Defense date: 2019-07-12

Examining board members

Helder Takashi Imoto Nakaya; Sergio Verjovski de Almeida; Edison Luiz Durigon; Daniela Santoro Rosa

• Advisor: Helder Takashi Imoto Nakaya

Abstract

Zika Virus (ZIKV) is an arbovirus that has gained high relevance in recent years. Although ZIKV infection generally induces mild symptoms, in some cases, the infection is associated to microcephaly in newborns and Guillain-Barré syndrome in adults. Long non-coding RNAs (lncRNAs) play a key role in modulating the immune system but nothing is known about their function in acute ZIKV infection. Therefore, the aim of this project was to study the transcriptome of infected Rhesus monkeys throughout the infection and how lncRNAs can alter the response in different mammals infected by ZIKV. We had infected four Rhesus monkeys with HS-2015-BA-01 strain and collected their blood before and after 1, 3, 5, 7, 10 and 14 days of infection. We then performed RNA-seq with whole blood samples to assess the transcriptional changes during infection. Our systems biology analyses revealed a regulation of immune response during the infection including the identification of many lncRNAs that were induced upon ZIKV infection. We identified around 9.210 lncRNAs, 3.246 of which werent annotated on the ENSEMBL database, and 140 of which were differentially expressed in some comparison. Some genes associated with immune response such as STAT1, JAK1 and IFNGR2, appear to be negatively regulated. Co-expression modules and network analyses have revealed the putative pathways and genes affected by these lncRNAs. Such as PROAP1, 2 and 3, not yet deposited in public banks, were highly correlated with BCL2, CYBA and MYCT1, that can potentially regulate pro-apoptotic response. In addition, other datasets (mice, neonates an cell culture) were used to further assess the importance and interference of lncRNAs in the infection. With this study we found many previously undescribed lncRNAs in the M. mulatta genome, some of which are correlated with important genes. Comparing all these results we found that some lncRNAs may play similar roles although in different animals. Overall, our results suggest that ZIKV infection modifies the expression of coding genes and lncRNAs that lead to apoptotic mechanisms against the virus. (AU)

• FAPESP's process: 18/10748-6 - Analysis of long non-coding RNAs in transcriptome of mammals infected with zika virus
• Grantee: Mariana Araújo Pereira
• Support Opportunities: Scholarships in Brazil - Master