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Alphavirus Transducing System: Tools for Visualizing Infection in Mosquito Vectors
Published on: November 24, 2010
Identification of mosquito proteins that differentially interact with alphavirus nonstructural protein 3, a
Nathaniel M Byers1, Paul L Burns1, Olga Stuchlik2
1Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, Fort Collins, Colorado, United States of America.
Abstract:
Chikungunya virus (CHIKV) and the closely related onyong-nyong virus (ONNV) are arthritogenic arboviruses that have caused significant, often debilitating, disease in millions of people. However, despite their kinship, they are vectored by different mosquito subfamilies that diverged 180 million years ago (anopheline versus culicine subfamilies). Previous work indicated that the nonstructural protein 3 (nsP3) of these alphaviruses was partially responsible for this vector specificity. To better understand the cellular components controlling alphavirus vector specificity, a cell culture model system of the anopheline restriction of CHIKV was developed along with a protein expression strategy. Mosquito proteins that differentially interacted with CHIKV nsP3 or ONNV nsP3 were identified. Six proteins were identified that specifically bound ONNV nsP3, ten that bound CHIKV nsP3 and eight that interacted with both. In addition to identifying novel factors that may play a role in virus/vector processing, these lists included host proteins that have been previously implicated as contributing to alphavirus replication.
Insights
Researchers identified mosquito proteins interacting with Chikungunya virus (CHIKV) and onyong-nyong virus (ONNV) nonstructural protein 3 (nsP3). This reveals host factors influencing arbovirus vector specificity and replication.
Area of Science:
- Virology and Molecular Biology
- Vector-borne Diseases
- Arthropod-borne Viruses (Arboviruses)
Background:
- Chikungunya virus (CHIKV) and onyong-nyong virus (ONNV) are arthritogenic arboviruses causing widespread human disease.
- These related alphaviruses exhibit distinct vector specificities, being transmitted by different mosquito subfamilies (anopheline vs. culicine).
- Previous studies suggested the nonstructural protein 3 (nsP3) of these viruses plays a role in determining vector specificity.
Purpose of the Study:
- To investigate the cellular components that mediate the vector specificity of CHIKV, particularly the restriction in anopheline mosquitoes.
- To identify mosquito proteins that differentially interact with the nsP3 proteins of CHIKV and ONNV.
- To understand the role of host-virus interactions in alphavirus replication and vector competence.
Main Methods:
- Development of a cell culture model system to study the anopheline restriction of CHIKV.
- Implementation of a protein expression strategy to produce viral nsP3 proteins.
- Identification of mosquito proteins that specifically bind to CHIKV nsP3 or ONNV nsP3 using interaction assays.
Main Results:
- Identification of six proteins that specifically bound ONNV nsP3.
- Identification of ten proteins that specifically bound CHIKV nsP3.
- Identification of eight proteins that interacted with both CHIKV and ONNV nsP3.
- The identified host proteins include factors previously implicated in alphavirus replication.
Conclusions:
- Novel host proteins involved in alphavirus/vector interactions and processing have been identified.
- These findings provide insights into the molecular mechanisms underlying alphavirus vector specificity.
- The study highlights the importance of host factors in determining the transmission dynamics of arboviruses like CHIKV and ONNV.
