Risk assessment of an Aedes flavivirus and its effect on pathogenic flavivirus replication in mosquitoes.

Abstract

Background: Mosquitoes are efficient vectors of medically significant flaviviruses and serve as hosts for insect-specific flaviviruses (ISFs). Aedes flavivirus (AEFV) is a classical ISF. Given the increasing discovery of ISFs, it is urgent to evaluate the potential risk of ISFs to human health as well as their impact on the transmission of pathogenic flaviviruses.

Methods: We isolated a strain of AEFV from wild Aedes albopictus populations in Hainan Province, China, using iodixanol density-gradient ultracentrifugation. The infection of the AEFV Hainan strain in Aedes, Culex, and four mammalian cell lines was investigated using fluorescence in situ hybridization (FISH) assays, and relative and absolute quantitative polymerase chain reaction (qPCR). Whether AEFV alters the vector competence of Ae. albopictus for pathogenic arboviruses and the underlying immune mechanisms were explored.

Results: The AEFV Hainan strain showed close genetic similarity to strains from Yunnan province of China, Thailand, and Peru. This strain was capable of infecting Ae. albopictus and Ae. aegypti but not Culex quinquefasciatus. Cell entry was the critical barrier for AEFV infection in Cx. quinquefasciatus cells. The infection risk of the AEFV Hainan strain in four mammalian cells (BHK-21, Vero, 293 T, and HeLa) was quite low due to the failure of cell entry or extremely limited replication. Prior infection of AEFV was detrimental to the replication of Zika virus and dengue virus serotype 2 in Ae. albopictus through activation of the Janus kinase/signal transducer and activator of transcription, Toll, or RNA interference pathway.

Conclusions: Our work excludes the risk of the AEFV Hainan strain to human health and highlights its potential as an immune inducer to sabotage Aedes mosquito ability for viral transmission.