Details

Autor(en) / Beteiligte

• O’Neill, Katelyn
• Olson, Bradley J. S. C.
• Huang, Ning
• Unis, Dave
• Clem, Rollie J.

Titel

Rapid selection against arbovirus-induced apoptosis during infection of a mosquito vector

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2015-03, Vol.112 (10), p.E1152-E1161

Ort / Verlag

United States: National Academy of Sciences

Erscheinungsjahr

2015

Quelle

Elektronische Zeitschriftenbibliothek (Open access)

Beschreibungen/Notizen

• Significance Understanding the factors that cause mosquitoes to resist arbovirus infection could lead to new strategies to control disease transmission. One antiviral response that may play a role in mosquito immunity is apoptosis, a type of cell suicide that is often induced by virus infection. However, apoptosis is rarely seen in arbovirus-infected mosquitoes. To understand why, we infected mosquitoes with an arbovirus that expresses a proapoptotic gene called reaper and found that the Reaper-expressing virus had replication defects in mosquitoes. We also observed strong selective pressure against retention of reaper in the virus genome. These results indicate that apoptosis is a strong antiviral response in mosquitoes and may explain why it is usually not observed in coevolved arbovirus–vector relationships. Millions of people are infected each year by arboviruses (arthropod-borne viruses) such as chikungunya, dengue, and West Nile viruses, yet for reasons that are largely unknown, only a relatively small number of mosquito species are able to transmit arboviruses. Understanding the complex factors that determine vector competence could facilitate strategies for controlling arbovirus infections. Apoptosis is a potential antiviral defense response that has been shown to be important in other virus–host systems. However, apoptosis is rarely seen in arbovirus-infected mosquito cells, raising questions about its importance as an antiviral defense in mosquitoes. We tested the effect of stimulating apoptosis during arbovirus infection by infecting Aedes aegypti mosquitoes with a Sindbis virus (SINV) clone called MRE/Rpr, in which the MRE-16 strain of SINV was engineered to express the proapoptotic gene reaper from Drosophila . MRE/Rpr exhibited an impaired infection phenotype that included delayed midgut infection, delayed virus replication, and reduced virus accumulation in saliva. Nucleotide sequencing of the reaper insert in virus populations isolated from individual mosquitoes revealed evidence of rapid and strong selection against maintenance of Reaper expression in MRE/Rpr-infected mosquitoes. The impaired phenotype of MRE/Rpr, coupled with the observed negative selection against Reaper expression, indicates that apoptosis is a powerful defense against arbovirus infection in mosquitoes and suggests that arboviruses have evolved mechanisms to avoid stimulating apoptosis in mosquitoes that serve as vectors.