10.1371/journal.pntd.0002107PLoS Neglected Tropical Diseases73

A Becerra

A Sabchareon

A Wilder-Smith

AJ Matlin

AM Nasirudeen

AM Ward

AW Tai

B Malewicz

B Pulendran

BJ Blencowe

C Balas

C Le Sommer

C Trapnell

CP Simmons

CS Villas-Boas

CY Huang

CY Yu

D Normile

DJ Gubler

DS Deluca

DS Shepard

EJ Nascimento

Eng Eong Ooi

ET Wang

Eva Harris

GF Silveira

HA Tissera

HT Long

HY Huang

I Umareddy

J Fink

J Pena

JA Suaya

JC Marioni

JL Kyle

Kenneth C. Goh

KJ Liew

LR Carrasco

LT Hoang

M Le Breton

MD Fernandez-Garcia

ME Beatty

MJ Schreiber

MM Moreno-Altamirano

MN Krishnan

October M. Sessions

OM Sessions

P Loke

Patrick Tan

Q Li

RV Warke

S Ubol

SB Halstead

Steve Rozen

T Tolfvenstam

TM Conceicao

Y Katz

Ying Tan

Yujing Liu

Z Wang

PLoS Neglected Tropical Diseases

PubMed

Dengue viruses 1-4 (DENV1-4) rely heavily on the host cell machinery to complete their life cycle, while at the same time evade the host response that could restrict their replication efficiency. These requirements may account for much of the broad gene-level changes to the host transcriptome upon DENV infection. However, host gene function is also regulated through transcriptional start site (TSS) selection and post-transcriptional modification to the RNA that give rise to multiple gene isoforms. The roles these processes play in the host response to dengue infection have not been explored. In the present study, we utilized RNA sequencing (RNAseq) to identify novel transcript variations in response to infection with both a pathogenic strain of DENV1 and its attenuated derivative. RNAseq provides the information necessary to distinguish the various isoforms produced from a single gene and their splice variants. Our data indicate that there is an extensive amount of previously uncharacterized TSS and post-transcriptional modifications to host RNA over a wide range of pathways and host functions in response to DENV infection. Many of the differentially expressed genes identified in this study have previously been shown to be required for flavivirus propagation and/or interact with DENV gene products. We also show here that the human transcriptome response to an infection by wild-type DENV or its attenuated derivative differs significantly. This differential response to wild-type and attenuated DENV infection suggests that alternative processing events may be part of a previously uncharacterized innate immune response to viral infection that is in large part evaded by wild-type DENV

Sessions, OM

Tan, Y

Goh, KC

Liu, Y

Tan, P

Rozen, S

Ooi, EE

University of Melbourne Institutional Repository

English

Host cell transcriptome profile during wild-type and attenuated dengue virus infection.

<div><p>Dengue viruses 1–4 (DENV1-4) rely heavily on the host cell machinery to complete their life cycle, while at the same time evade the host response that could restrict their replication efficiency. These requirements may account for much of the broad gene-level changes to the host transcriptome upon DENV infection. However, host gene function is also regulated through transcriptional start site (TSS) selection and post-transcriptional modification to the RNA that give rise to multiple gene isoforms. The roles these processes play in the host response to dengue infection have not been explored. In the present study, we utilized RNA sequencing (RNAseq) to identify novel transcript variations in response to infection with both a pathogenic strain of DENV1 and its attenuated derivative. RNAseq provides the information necessary to distinguish the various isoforms produced from a single gene and their splice variants. Our data indicate that there is an extensive amount of previously uncharacterized TSS and post-transcriptional modifications to host RNA over a wide range of pathways and host functions in response to DENV infection. Many of the differentially expressed genes identified in this study have previously been shown to be required for flavivirus propagation and/or interact with DENV gene products. We also show here that the human transcriptome response to an infection by wild-type DENV or its attenuated derivative differs significantly. This differential response to wild-type and attenuated DENV infection suggests that alternative processing events may be part of a previously uncharacterized innate immune response to viral infection that is in large part evaded by wild-type DENV.</p> </div

October M. Sessions (389415)

Ying Tan (346135)

Kenneth C. Goh (389416)

Yujing Liu (389417)

Patrick Tan (18147)

Steve Rozen (134498)

Eng Eong Ooi (56879)

The Francis Crick Institute

Host Cell Transcriptome Profile during Wild-Type and Attenuated Dengue Virus Infection

Host Cell Transcriptome Profile during Wild-Type and Attenuated Dengue Virus Infection

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