Dataset Information

Analysis of the virus propagation profile of 14 dengue virus isolates in Aedes albopictus C6/36 cells.

ABSTRACT: OBJECTIVE:The mosquito transmitted RNA virus dengue virus (DENV) shows significant variation as a consequence of the lack of proofreading activity of the RNA-dependent RNA polymerase that synthesizes new virus genomes. How this variation affects DENV replication, and how this in turn impacts drug development remains largely unknown. Given the technical limitations in working with large numbers of isolates few studies have sought to investigate this area. This study used a panel of 14 DENV isolates of different serotypes and origins to determine how much virus replication in Aedes albopictus C6/36 cells was affected by DENV variability. RESULTS:The results showed that there was considerable variation, with peak titers ranging from 6Log10 to 8Log10, and maximum titer being reached from day 3 to day 9 post infection. While strains from DENV 1 and 4 serotypes showed considerable uniformity, DENV 2 and 3 strains showed much greater variation. Overall, these results show that serotype specific strain variation can have a significant impact on DENV replication, suggesting that studies either investigating DENV pathogenesis or developing drug therapeutics should consider the contribution of DENV variability.

SUBMITTER: Hitakarun A

PROVIDER: S-EPMC7552352 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Analysis of the virus propagation profile of 14 dengue virus isolates in Aedes albopictus C6/36 cells.

Hitakarun Atitaya A Ramphan Suwipa S Wikan Nitwara N Smith Duncan R DR

BMC research notes 20201012 1

<h4>Objective</h4>The mosquito transmitted RNA virus dengue virus (DENV) shows significant variation as a consequence of the lack of proofreading activity of the RNA-dependent RNA polymerase that synthesizes new virus genomes. How this variation affects DENV replication, and how this in turn impacts drug development remains largely unknown. Given the technical limitations in working with large numbers of isolates few studies have sought to investigate this area. This study used a panel of 14 DEN ...[more]

PMID: 33046135

Similar Datasets

Project description:Dengue virus (DENV) causes frequent epidemics infecting ∼390 million people annually in over 100 countries. There are no approved vaccines or antiviral drugs for treatment of infected patients. However, there is a novel approach to control DENV transmission by the mosquito vectors, Aedes aegypti and Aedes albopictus, using the Wolbachia symbiont. The wMelPop strain of Wolbachia suppresses DENV transmission and shortens the mosquito life span. However, the underlying mechanism is poorly understood. To clarify this mechanism, either naive A. albopictus (C6/36) or wMelPop-C6/36 cells were infected with DENV serotype 2 (DENV2). Analysis of host transcript profiles by transcriptome sequencing (RNAseq) revealed that the presence of wMelPop dramatically altered the mosquito host cell transcription in response to DENV2 infection. The viral RNA evolved from wMelPop-C6/36 cells contained low-frequency mutations (∼25%) within the coding region of transmembrane domain 1 (TMD1) of E protein. Mutations with >97% frequencies were distributed within other regions of E, the NS5 RNA-dependent RNA polymerase (NS5POL) domain, and the TMDs of NS2A, NS2B, and NS4B. Moreover, while DENV2-infected naive C6/36 cells showed syncytium formation, DENV2-infected wMelPop-C6/36 cells did not. The Wolbachia-induced mutant DENV2 can readily infect and replicate in naive C6/36 cells, whereas in mutant DENV2-infected BHK-21 or Vero cells, virus replication was delayed. In LLC-MK2 cells, the mutant failed to produce plaques. Additionally, in BHK-21 cells, many mutations in the viral genome reverted to the wild type (WT) and compensatory mutations in NS3 gene appeared. Our results indicate that wMelPop impacts significantly the interactions of DENV2 with mosquito and mammalian host cells.IMPORTANCE Mosquito-borne diseases are of global significance causing considerable morbidity and mortality throughout the world. Dengue virus (DENV; serotypes 1 to 4), a member of the Flavivirus genus of the Flaviviridae family, causes millions of infections annually. Development of a safe vaccine is hampered due to absence of cross-protection and increased risk in secondary infections due to antibody-mediated immune enhancement. Infection of vector mosquitoes with Wolbachia bacteria offers a novel countermeasure to suppress DENV transmission, but the mechanisms are poorly understood. In this study, the host transcription profiles and viral RNA sequences were analyzed in naive A. albopictus (C6/36) and wMelPop-C6/36 cells by RNAseq. Our results showed that the wMelPop symbiont caused profound changes in host transcription profiles and morphology of DENV2-infected C6/36 cells. Accumulation of several mutations throughout DENV2 RNA resulted in loss of infectivity of progeny virions. Our findings offer new insights into the mechanism of Wolbachia-mediated suppression of DENV transmission.

Dataset Information

Analysis of the virus propagation profile of 14 dengue virus isolates in Aedes albopictus C6/36 cells.

Publications

Analysis of the virus propagation profile of 14 dengue virus isolates in Aedes albopictus C6/36 cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets