Insect response to alphavirus infection—Establishment of alphavirus persistence in insect cells involves inhibition of viral polyprotein cleavage

Mudiganti, Usharani; Hernandez, Raquel; Brown, Dennis T.

doi:10.1016/j.virusres.2010.02.016

Cited by 20 publications

(27 citation statements)

References 75 publications

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“…The arthropod immune system consists of the RNAi pathway, as well as the Toll, Imd, and Jak-STAT signaling pathways, which result in changes in the transcriptome leading to the production of proviral and antiviral factors. Previously published microarray studies have reported many genes that are regulated in response to alpha-and flavivirus infections in Drosophila S2 cells, Aedes aegypti midguts, and whole Aedes aegypti mosquitoes (25,42,43). In the present study we identified 95 genes with significantly altered expression as a result of SINV replication in whole Drosophila.…”

Section: Discussionmentioning

confidence: 58%

“…Previously, totA and other tot family members were shown to be upregulated in response to cellular stress (47,48). Other identified genes such as tepI, tepII, and raf code for proteins involved in phagocytosis, opsonization, and hemocyte proliferation in response to Gram-negative bacterial infection (25,49,50). During DCV or dengue virus infections, the Jak-STAT pathway was shown to be activated and induce the transcription of vir-1 or DVRFs, respectively (23,24).…”

Section: Discussionmentioning

confidence: 99%

“…In both Drosophila and mosquitoes, knockdowns and mutations in the Jak-kinase led to an increase in viral infection, indicating an antiviral response involving the Jak-STAT pathway, presumably as a result of STAT-dependent expression of an antiviral effector molecule (23,24). When considering a specific response to virus infection, certain downstream molecules, vir-1, tepII, and DVRF1 and DVRF2, have been shown to be upregulated by various viruses (23)(24)(25).…”

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confidence: 99%

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An Antiviral Role for Antimicrobial Peptides during the Arthropod Response to Alphavirus Replication

Huang

Kingsolver

Avadhanula

et al. 2013

J Virol

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Alphaviruses establish a persistent infection in arthropod vectors which is essential for the effective transmission of the virus to vertebrate hosts. The development of persistence in insects is not well understood, although it is thought to involve the innate immune response. Using a transgenic fly system expressing a self-replicating viral RNA genome analog, we have previously demonstrated antiviral roles of the Drosophila Imd (immune deficiency) and Jak-STAT innate immunity pathways in response to alphavirus replication. In the present study, comparative microarray analysis of flies harboring an alphavirus replicon and control green fluorescent protein flies identified 95 SINrep-sensitive genes. Furthermore, a subset of these genes is regulated by Rel or STAT transcription factors of the Imd and Jak-STAT pathways, respectively. We identified two antimicrobial peptide genes, attC and dptB, which are SINrep sensitive and regulated by STAT and Rel, respectively. SINrep flies heterozygous for attC had an increased viral RNA level, while knocking down dptB in SINrep flies resulted in impaired development. When injected with whole virus, the double-stranded RNA knockdowns of either attC or dptB showed a significant increase in virus titers. Our data demonstrate an antiviral response involving the Imd and Jak-STAT mediated expression of dptB and attC.

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Section: Discussionmentioning

confidence: 58%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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An Antiviral Role for Antimicrobial Peptides during the Arthropod Response to Alphavirus Replication

Huang

Kingsolver

Avadhanula

et al. 2013

J Virol

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“…Although these experiments need to be confirmed in vivo, they suggest an innate immune role for Mcr. Consistent with this idea, Mudiganti et al (Mudiganti et al, 2010) found that both Tep2 and Mcr were significantly upregulated 5 days after infection with the alphavirus Sindbis. Perhaps Mcr expressed in hemocytes plays a primary role in the surveillance of pathogens in the hemocoel, which is in contact with the basal surfaces of all ectodermal epithelia, whereas Mcr expressed on the apical plasma membrane of ectodermal cells can provide a similar function in those compartments in direct contact with the outside world.…”

Section: Mcr In Innate Immunitymentioning

confidence: 72%

Macroglobulin complement-relatedencodes a protein required for septate junction organization and paracellular barrier function inDrosophila

et al. 2014

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Polarized epithelia play crucial roles as barriers to the outside environment and enable the formation of specialized compartments for organs to carry out essential functions. Barrier functions are mediated by cellular junctions that line the lateral plasma membrane between cells, principally tight junctions in vertebrates and septate junctions (SJs) KEY WORDS: Septate junction, Epithelia, Innate immunity INTRODUCTIONPolarized epithelia play crucial roles as barriers to the outside world and in providing distinct compartments for organs to carry out essential metabolic functions in all metazoans. These functions require a physiologically tight epithelium to provide a barrier to the flow of small molecules between the apical and basal sides of the epithelium. This paracellular barrier is established and maintained by tight junctions (TJs) in the epithelia of vertebrate organisms, and by septate junctions (SJs) in invertebrate organisms. TJs localize

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“…Viral infection leads to the rapid induction of an antiviral transcriptional response (14,15,40,41). In metazoans, RNAPII recruitment and activation are known to regulate signal-dependent gene transcription (9,42,43); however, the factors involved in recruiting and stabilizing RNAPII at the promoter in a contextand gene-specific manner in response to diverse stimuli, including viral infection, are unclear.…”

Section: Discussionmentioning

confidence: 99%

Nup98 promotes antiviral gene expression to restrict RNA viral infection in Drosophila

Panda

Pascual-Garcia²,

Dunagin

et al. 2014

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

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In response to infection, the innate immune system rapidly activates an elaborate and tightly orchestrated gene expression program to induce critical antimicrobial genes. While many key players in this program have been identified in disparate biological systems, it is clear that there are additional uncharacterized mechanisms at play. Our previous studies revealed that a rapidly-induced antiviral gene expression program is active against disparate human arthropod-borne viruses in Drosophila. Moreover, one-half of this program is regulated at the level of transcriptional pausing. Here we found that Nup98, a virus-induced gene, was antiviral against a panel of viruses both in cells and adult flies since its depletion significantly enhanced viral infection. Mechanistically, we found that Nup98 promotes antiviral gene expression in Drosophila at the level of transcription. Expression profiling revealed that the virus-induced activation of 36 genes was abrogated upon loss of Nup98; and we found that a subset of these Nup98-dependent genes were antiviral. These Nup98-dependent virus-induced genes are Cdk9-dependent and translation-independent suggesting that these are rapidly induced primary response genes. Biochemically, we demonstrate that Nup98 is directly bound to the promoters of virus-induced genes, and that it promotes occupancy of the initiating form of RNA polymerase II at these promoters, which are rapidly induced on viral infection to restrict human arboviruses in insects.innate immunity | nuclear pore | nucleoporin | pol II regulation | P-TEFb

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Insect response to alphavirus infection—Establishment of alphavirus persistence in insect cells involves inhibition of viral polyprotein cleavage

Cited by 20 publications

References 75 publications

An Antiviral Role for Antimicrobial Peptides during the Arthropod Response to Alphavirus Replication

An Antiviral Role for Antimicrobial Peptides during the Arthropod Response to Alphavirus Replication

Macroglobulin complement-relatedencodes a protein required for septate junction organization and paracellular barrier function inDrosophila

Nup98 promotes antiviral gene expression to restrict RNA viral infection in Drosophila

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