<i>Dishevelled</i> Has Anti-Viral Activity in Rift Valley Fever Virus Infected <i>Aedes aegypti</i>
Mosquitoes in the genera <i>Aedes</i> and <i>Culex</i> are vectors of Rift Valley fever virus (RVFV), which emerges in periodic epidemics in Africa and Saudi Arabia. Factors that influence the transmission dynamics of RVFV are not well characterized. To address this, we inter...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-10-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/15/11/2140 |
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| author | Christian B. Smith Natasha F. Hodges Rebekah C. Kading Corey L. Campbell |
| author_facet | Christian B. Smith Natasha F. Hodges Rebekah C. Kading Corey L. Campbell |
| author_sort | Christian B. Smith |
| collection | DOAJ |
| description | Mosquitoes in the genera <i>Aedes</i> and <i>Culex</i> are vectors of Rift Valley fever virus (RVFV), which emerges in periodic epidemics in Africa and Saudi Arabia. Factors that influence the transmission dynamics of RVFV are not well characterized. To address this, we interrogated mosquito host-signaling responses through analysis of differentially expressed genes (DEGs) in two mosquito species with marked differences in RVFV vector competence: <i>Aedes aegypti</i> (<i>Aae</i>, low competence) and <i>Culex tarsalis</i> (<i>Cxt</i>, high competence). Mosquito–host transcripts related to three different signaling pathways were investigated. Selected genes from the Wingless (Wg, WNT-beta-catenin) pathway, which is a conserved regulator of cell proliferation and differentiation, were assessed. One of these, <i>dishevelled</i> (<i>DSH</i>), differentially regulates progression/inhibition of the WNT and JNK (c-Jun N-terminal Kinase) pathways. A negative regulator of the JNK-signaling pathway, puckered, was also assessed. Lastly, Janus kinase/signal transducers and activators of transcription (JAK-STAT) are important for innate immunity; in this context, we tested domeless levels. Here, individual <i>Aae</i> and <i>Cxt</i> were exposed to RVFV MP-12 via oral bloodmeals and held for 14 days. Robust decreases in DEGs in both <i>Aae</i> and <i>Cxt</i> were observed. In particular, <i>Aae DSH</i> expression, but not <i>Cxt DSH</i>, was correlated to the presence/absence of viral RNA at 14 days post-challenge (dpc). Moreover, there was an inverse relationship between the viral copy number and <i>aaeDSH</i> expression. <i>DSH</i> silencing resulted in increased viral copy numbers compared to controls at 3 dpc, consistent with a role for <i>aaeDSH</i> in antiviral immunity. Analysis of cis-regulatory regions for the genes of interest revealed clues to upstream regulation of these pathways. |
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| id | doaj.art-47d97c7e66e14a60a0d9243f5c48af17 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-09T16:23:31Z |
| publishDate | 2023-10-01 |
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| spelling | doaj.art-47d97c7e66e14a60a0d9243f5c48af172023-11-24T15:10:32ZengMDPI AGViruses1999-49152023-10-011511214010.3390/v15112140<i>Dishevelled</i> Has Anti-Viral Activity in Rift Valley Fever Virus Infected <i>Aedes aegypti</i>Christian B. Smith0Natasha F. Hodges1Rebekah C. Kading2Corey L. Campbell3Center for Vector-Borne Infectious Diseases, Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USACenter for Vector-Borne Infectious Diseases, Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USACenter for Vector-Borne Infectious Diseases, Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USACenter for Vector-Borne Infectious Diseases, Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USAMosquitoes in the genera <i>Aedes</i> and <i>Culex</i> are vectors of Rift Valley fever virus (RVFV), which emerges in periodic epidemics in Africa and Saudi Arabia. Factors that influence the transmission dynamics of RVFV are not well characterized. To address this, we interrogated mosquito host-signaling responses through analysis of differentially expressed genes (DEGs) in two mosquito species with marked differences in RVFV vector competence: <i>Aedes aegypti</i> (<i>Aae</i>, low competence) and <i>Culex tarsalis</i> (<i>Cxt</i>, high competence). Mosquito–host transcripts related to three different signaling pathways were investigated. Selected genes from the Wingless (Wg, WNT-beta-catenin) pathway, which is a conserved regulator of cell proliferation and differentiation, were assessed. One of these, <i>dishevelled</i> (<i>DSH</i>), differentially regulates progression/inhibition of the WNT and JNK (c-Jun N-terminal Kinase) pathways. A negative regulator of the JNK-signaling pathway, puckered, was also assessed. Lastly, Janus kinase/signal transducers and activators of transcription (JAK-STAT) are important for innate immunity; in this context, we tested domeless levels. Here, individual <i>Aae</i> and <i>Cxt</i> were exposed to RVFV MP-12 via oral bloodmeals and held for 14 days. Robust decreases in DEGs in both <i>Aae</i> and <i>Cxt</i> were observed. In particular, <i>Aae DSH</i> expression, but not <i>Cxt DSH</i>, was correlated to the presence/absence of viral RNA at 14 days post-challenge (dpc). Moreover, there was an inverse relationship between the viral copy number and <i>aaeDSH</i> expression. <i>DSH</i> silencing resulted in increased viral copy numbers compared to controls at 3 dpc, consistent with a role for <i>aaeDSH</i> in antiviral immunity. Analysis of cis-regulatory regions for the genes of interest revealed clues to upstream regulation of these pathways.https://www.mdpi.com/1999-4915/15/11/2140vector biologyanti-viral immunitycell signalingvector competencetranscriptional regulation |
| spellingShingle | Christian B. Smith Natasha F. Hodges Rebekah C. Kading Corey L. Campbell <i>Dishevelled</i> Has Anti-Viral Activity in Rift Valley Fever Virus Infected <i>Aedes aegypti</i> Viruses vector biology anti-viral immunity cell signaling vector competence transcriptional regulation |
| title | <i>Dishevelled</i> Has Anti-Viral Activity in Rift Valley Fever Virus Infected <i>Aedes aegypti</i> |
| title_full | <i>Dishevelled</i> Has Anti-Viral Activity in Rift Valley Fever Virus Infected <i>Aedes aegypti</i> |
| title_fullStr | <i>Dishevelled</i> Has Anti-Viral Activity in Rift Valley Fever Virus Infected <i>Aedes aegypti</i> |
| title_full_unstemmed | <i>Dishevelled</i> Has Anti-Viral Activity in Rift Valley Fever Virus Infected <i>Aedes aegypti</i> |
| title_short | <i>Dishevelled</i> Has Anti-Viral Activity in Rift Valley Fever Virus Infected <i>Aedes aegypti</i> |
| title_sort | i dishevelled i has anti viral activity in rift valley fever virus infected i aedes aegypti i |
| topic | vector biology anti-viral immunity cell signaling vector competence transcriptional regulation |
| url | https://www.mdpi.com/1999-4915/15/11/2140 |
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