Aedes aegyptiuses RNA interference in defense against Sindbis virus infection

Campbell, Corey L.; Keene, Kimberly M.; Brackney, Douglas E.; Olson, Ken E.; Blair, Carol D.; Wilusz, Jeffrey; Foy, Brian D.

doi:10.1186/1471-2180-8-47

Cited by 213 publications

(242 citation statements)

References 52 publications

(59 reference statements)

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“…Certainly, immune response may also play an important role in low-level DENV-2 replication in intrathoracically inoculated mosquito midgut because of innate immune response to arbovirus infection in this organ. 33,[37][38][39][40] Additionally, the always increased replication profiles of DENV-2 RNA and E protein in intrathoracically inoculated mosquito midgut also suggest that the progeny viruses released from orally infected midgut can reversely infect this organ; when the virus replication in orally infected midgut declines, this may be equal to another infectious blood meal. It is probably one of the reasons why the mosquito is a life-long carrier and transmitter of dengue viruses after it is infected by the virus.…”

Section: Discussionmentioning

confidence: 99%

Quantitative Analysis of Replication and Tropisms of Dengue Virus Type 2 in Aedes albopictus

Zhang

Zheng²,

Yu³

et al. 2010

The American Society of Tropical Medicine and Hygiene

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Dengue virus serotype 2 (DENV-2) RNA replication profiles and tropisms were studied by using quantitative RT-PCR (q-RTPCR) in intrathoracically infected Aedes albopictus. The virus RNA replication profiles were diverse in mosquito organs. In fat body, brain, salivary gland, and malpighian tubes, it peaked at 8, 23, 23, and 27 days post-infection, respectively, and then, all declined. In midgut, it increased all the time and had no trend of decline. In ovary, it had no apparent increase. Subsequent Western blotting of DENV-2 E protein had similar results. Using ribosomal protein 7 (rpS7) as an internal control, we found that, in salivary gland, brain, fat body, and midgut, the average DENV-2 RNA levels (DENV-2 RNA/rpS7 mRNA) were 1,028, 464, 5.6, and 6.2, respectively; in malpighian tubes, it was 1, and in ovary, it was far less than 1. These results suggest that infection profiles and tropism of DENV-2 RNA in Ae. albopictus organs are significantly different.

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Section: Discussionmentioning

confidence: 99%

Quantitative Analysis of Replication and Tropisms of Dengue Virus Type 2 in Aedes albopictus

Zhang

Zheng²,

Yu³

et al. 2010

The American Society of Tropical Medicine and Hygiene

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“…Aag-2 cells, derived from these mosquitoes, are permissive to RVFV and amenable to robust RNAi ( Fig. 3E; Campbell et al 2008;Moutailler et al 2011). There are two annotated Dcp2 orthologs in the A. aegypti genome (AAEL015607 and AAEL000783) with 99% amino acid sequence identity, allowing us to design a single dsRNA targeting a conserved region of both Dcp2 genes to deplete both simultaneously.…”

Section: Decapping Restricts Rvfv In Aedes Aegypti Mosquito Cellsmentioning

confidence: 99%

A genome-wide RNAi screen reveals that mRNA decapping restricts bunyaviral replication by limiting the pools of Dcp2-accessible targets for cap-snatching

et al. 2013

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Bunyaviruses are an emerging group of medically important viruses, many of which are transmitted from insects to mammals. To identify host factors that impact infection, we performed a genome-wide RNAi screen in Drosophila and identified 131 genes that impacted infection of the mosquito-transmitted bunyavirus Rift Valley fever virus (RVFV). Dcp2, the catalytic component of the mRNA decapping machinery, and two decapping activators, DDX6 and LSM7, were antiviral against disparate bunyaviruses in both insect cells and adult flies. Bunyaviruses 59 cap their mRNAs by ''cap-snatching'' the 59 ends of poorly defined host mRNAs. We found that RVFV cap-snatches the 59 ends of Dcp2 targeted mRNAs, including cell cycle-related genes. Loss of Dcp2 allows increased viral transcription without impacting viral mRNA stability, while ectopic expression of Dcp2 impedes viral transcription. Furthermore, arresting cells in late S/early G2 led to increased Dcp2 mRNA targets and increased RVFV replication. Therefore, RVFV competes for the Dcp2-accessible mRNA pool, which is dynamically regulated and can present a bottleneck for viral replication.

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“…To be transmitted to another host, the virus must replicate in the salivary glands and be expelled in the saliva during a subsequent blood meal (7,8). In addition to overcoming physical barriers in the mosquito vector, the virus must also defeat innate immune defenses such as the Toll and JAK/STAT pathways and RNA interference (9)(10)(11)(12)(13). Although progress has been made in understanding antiviral immune mechanisms in mosquitoes in recent years, our knowledge is still far from complete.…”

mentioning

confidence: 99%

Rapid selection against arbovirus-induced apoptosis during infection of a mosquito vector

O’Neill

Olson

Huang

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Millions of people are infected each year by arboviruses (arthropod-borne viruses) such as chikungunya, dengue, and West Nile viruses, yet for reasons that are largely unknown, only a relatively small number of mosquito species are able to transmit arboviruses. Understanding the complex factors that determine vector competence could facilitate strategies for controlling arbovirus infections. Apoptosis is a potential antiviral defense response that has been shown to be important in other virus-host systems. However, apoptosis is rarely seen in arbovirus-infected mosquito cells, raising questions about its importance as an antiviral defense in mosquitoes. We tested the effect of stimulating apoptosis during arbovirus infection by infecting Aedes aegypti mosquitoes with a Sindbis virus (SINV) clone called MRE/Rpr, in which the MRE-16 strain of SINV was engineered to express the proapoptotic gene reaper from Drosophila. MRE/Rpr exhibited an impaired infection phenotype that included delayed midgut infection, delayed virus replication, and reduced virus accumulation in saliva. Nucleotide sequencing of the reaper insert in virus populations isolated from individual mosquitoes revealed evidence of rapid and strong selection against maintenance of Reaper expression in MRE/Rpr-infected mosquitoes. The impaired phenotype of MRE/Rpr, coupled with the observed negative selection against Reaper expression, indicates that apoptosis is a powerful defense against arbovirus infection in mosquitoes and suggests that arboviruses have evolved mechanisms to avoid stimulating apoptosis in mosquitoes that serve as vectors.apoptosis | arbovirus | mosquito | vector competence

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Aedes aegyptiuses RNA interference in defense against Sindbis virus infection

Cited by 213 publications

References 52 publications

Quantitative Analysis of Replication and Tropisms of Dengue Virus Type 2 in Aedes albopictus

Quantitative Analysis of Replication and Tropisms of Dengue Virus Type 2 in Aedes albopictus

A genome-wide RNAi screen reveals that mRNA decapping restricts bunyaviral replication by limiting the pools of Dcp2-accessible targets for cap-snatching

Rapid selection against arbovirus-induced apoptosis during infection of a mosquito vector

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