Genetic Adaptation by Dengue Virus Serotype 2 to Enhance Infection of <i>Aedes aegypti</i> Mosquito Midguts
Dengue viruses (DENVs), serotypes 1–4, are arthropod-borne viruses transmitted to humans by mosquitoes, primarily Aedes aegypti. The transmission cycle begins when <i>Ae. aegypti</i> ingest blood from a viremic human and the virus infects midgut epithelial cells. In studying viruses deri...
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MDPI AG
2022-07-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/14/7/1569 |
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| author | Steven M. Erb Siritorn Butrapet John T. Roehrig Claire Y.-H. Huang Carol D. Blair |
| author_facet | Steven M. Erb Siritorn Butrapet John T. Roehrig Claire Y.-H. Huang Carol D. Blair |
| author_sort | Steven M. Erb |
| collection | DOAJ |
| description | Dengue viruses (DENVs), serotypes 1–4, are arthropod-borne viruses transmitted to humans by mosquitoes, primarily Aedes aegypti. The transmission cycle begins when <i>Ae. aegypti</i> ingest blood from a viremic human and the virus infects midgut epithelial cells. In studying viruses derived from the DENV2 infectious clone 30P-NBX, we found that when the virus was delivered to female <i>Ae. aegypti</i> in an infectious blood meal, the midgut infection rate (MIR) was very low. To determine if adaptive mutations in the DENV2 envelope (E) glycoprotein could be induced to increase the MIR, we serially passed 30P-NBX in <i>Ae. aegypti</i> midguts. After four passages, a single, non-conservative mutation in E protein domain II (DII) nucleotide position 1300 became dominant, resulting in replacement of positively-charged amino acid lysine (K) at position 122 with negatively-charged glutamic acid (E; K122E) and a significantly-enhanced MIR. Site directed mutagenesis experiments showed that reducing the positive charge of this surface-exposed region of the E protein DII correlated with improved <i>Ae. aegypti</i> midgut infection. |
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| format | Article |
| id | doaj.art-eb6e14df614b47c3af4df3df0f058344 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-09T05:41:43Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
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| series | Viruses |
| spelling | doaj.art-eb6e14df614b47c3af4df3df0f0583442023-12-03T12:24:40ZengMDPI AGViruses1999-49152022-07-01147156910.3390/v14071569Genetic Adaptation by Dengue Virus Serotype 2 to Enhance Infection of <i>Aedes aegypti</i> Mosquito MidgutsSteven M. Erb0Siritorn Butrapet1John T. Roehrig2Claire Y.-H. Huang3Carol D. Blair4Center for Vector-Borne Infectious Diseases, Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO 80523, USADivision of Vector-Borne Diseases, Centers for Disease Control and Prevention, Fort Collins, CO 80521, USADivision of Vector-Borne Diseases, Centers for Disease Control and Prevention, Fort Collins, CO 80521, USADivision of Vector-Borne Diseases, Centers for Disease Control and Prevention, Fort Collins, CO 80521, USACenter for Vector-Borne Infectious Diseases, Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO 80523, USADengue viruses (DENVs), serotypes 1–4, are arthropod-borne viruses transmitted to humans by mosquitoes, primarily Aedes aegypti. The transmission cycle begins when <i>Ae. aegypti</i> ingest blood from a viremic human and the virus infects midgut epithelial cells. In studying viruses derived from the DENV2 infectious clone 30P-NBX, we found that when the virus was delivered to female <i>Ae. aegypti</i> in an infectious blood meal, the midgut infection rate (MIR) was very low. To determine if adaptive mutations in the DENV2 envelope (E) glycoprotein could be induced to increase the MIR, we serially passed 30P-NBX in <i>Ae. aegypti</i> midguts. After four passages, a single, non-conservative mutation in E protein domain II (DII) nucleotide position 1300 became dominant, resulting in replacement of positively-charged amino acid lysine (K) at position 122 with negatively-charged glutamic acid (E; K122E) and a significantly-enhanced MIR. Site directed mutagenesis experiments showed that reducing the positive charge of this surface-exposed region of the E protein DII correlated with improved <i>Ae. aegypti</i> midgut infection.https://www.mdpi.com/1999-4915/14/7/1569dengue viruses<i>Aedes aegypti</i>adaptive mutation |
| spellingShingle | Steven M. Erb Siritorn Butrapet John T. Roehrig Claire Y.-H. Huang Carol D. Blair Genetic Adaptation by Dengue Virus Serotype 2 to Enhance Infection of <i>Aedes aegypti</i> Mosquito Midguts Viruses dengue viruses <i>Aedes aegypti</i> adaptive mutation |
| title | Genetic Adaptation by Dengue Virus Serotype 2 to Enhance Infection of <i>Aedes aegypti</i> Mosquito Midguts |
| title_full | Genetic Adaptation by Dengue Virus Serotype 2 to Enhance Infection of <i>Aedes aegypti</i> Mosquito Midguts |
| title_fullStr | Genetic Adaptation by Dengue Virus Serotype 2 to Enhance Infection of <i>Aedes aegypti</i> Mosquito Midguts |
| title_full_unstemmed | Genetic Adaptation by Dengue Virus Serotype 2 to Enhance Infection of <i>Aedes aegypti</i> Mosquito Midguts |
| title_short | Genetic Adaptation by Dengue Virus Serotype 2 to Enhance Infection of <i>Aedes aegypti</i> Mosquito Midguts |
| title_sort | genetic adaptation by dengue virus serotype 2 to enhance infection of i aedes aegypti i mosquito midguts |
| topic | dengue viruses <i>Aedes aegypti</i> adaptive mutation |
| url | https://www.mdpi.com/1999-4915/14/7/1569 |
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