The role of midgut serine proteases in Aedes aegypti vector competence
| dc.contributor.author | Brackney, Douglas Eugene, author | |
| dc.contributor.author | Olson, Kenneth E., advisor | |
| dc.date.accessioned | 2024-03-13T18:50:53Z | |
| dc.date.available | 2024-03-13T18:50:53Z | |
| dc.date.issued | 2007 | |
| dc.description.abstract | Numerous gut-associated viruses utilize host proteolytic enzymes to facilitate enhancement of infection. Similarly, arboviruses infecting the invertebrate host (vector) through the alimentary tract may exploit serine proteases in the midgut to enhance vector infection. Recent genetic and biochemical experiments have demonstrated that dengue virus type 2 (DENV-2) may require proteolytic processing by midgut trypsins to efficiently infect Aedes aegypti. These results suggest midgut serine proteases may influence A. aegypti vector competence. The requirement of serine proteases in DENV-2 infection of the vector provides unique targets for development of novel control strategies through approaches such as transmission blocking vaccines. | |
| dc.description.abstract | Transmission blocking vaccines targeting two midgut serine proteases were developed and assessed for their ability to block DENV-2 infection of A. aegypti. This study found that DENV-2 infected the midgut more efficiently when anti-abundant trypsin (AT) immune serum was mixed with an infectious bloodmeal. | |
| dc.description.abstract | To further investigate the importance of proteolytic processing of DENV-2, multiple mutant viruses lacking potential trypsin recognition sites within domain III of the major surface envelope glycoprotein (E) were constructed. It was demonstrated that deletion of one of these sites (K305) increased the ability of the virus to infect the mosquito. Furthermore, co-feeding wild-type DENV-2 with trypsin inhibitors increased midgut infection rates. Interestingly, suppression of each serine protease alone by RNA interference had no effect on infection rates. Overall these results suggest that serine proteases within the mosquito midgut do not proteolytically activate, but may limit DENV-2 infectivity of A. aegypti. | |
| dc.description.abstract | The RNA interference studies also reveal that one midgut protease, AT, may not be a traditional serine protease. These results were supported by phylogenetic analysis and sequence alignment data of multiple insect serine proteases. It was determined that AT may represent the first mosquito serine collagenase to be identified. | |
| dc.description.abstract | In total, this work highlights the complexity of mosquito digestion and its effects on DENV-2 infectivity and offers new insight into the basic physiology of mosquito digestion. | |
| dc.format.medium | born digital | |
| dc.format.medium | doctoral dissertations | |
| dc.identifier | ETDF_Brackney_2007_3299760.pdf | |
| dc.identifier.uri | https://hdl.handle.net/10217/237597 | |
| dc.language | English | |
| dc.language.iso | eng | |
| dc.publisher | Colorado State University. Libraries | |
| dc.relation.ispartof | 2000-2019 | |
| dc.rights | Copyright and other restrictions may apply. User is responsible for compliance with all applicable laws. For information about copyright law, please see https://libguides.colostate.edu/copyright. | |
| dc.rights.license | Per the terms of a contractual agreement, all use of this item is limited to the non-commercial use of Colorado State University and its authorized users. | |
| dc.subject | Aedes aegypti | |
| dc.subject | serine proteases | |
| dc.subject | vector competence | |
| dc.subject | organismal biology | |
| dc.subject | parasitology | |
| dc.subject | virology | |
| dc.subject | entomology | |
| dc.title | The role of midgut serine proteases in Aedes aegypti vector competence | |
| dc.type | Text | |
| dcterms.rights.dpla | This Item is protected by copyright and/or related rights (https://rightsstatements.org/vocab/InC/1.0/). You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s). | |
| thesis.degree.discipline | Microbiology, Immunology, and Pathology | |
| thesis.degree.grantor | Colorado State University | |
| thesis.degree.level | Doctoral | |
| thesis.degree.name | Doctor of Philosophy (Ph.D.) |
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