Cotton leaf curl Multan virus differentially regulates innate antiviral immunity of whitefly ( Bemisia tabaci ) vector to promote cryptic species-dependent virus acquisition

Begomoviruses represent the largest group of economically important, highly pathogenic, DNA plant viruses that contribute a substantial amount of global crop disease burden. The exclusive transmission of begomoviruses by whiteflies ( ) requires them to interact and efficiently manipulate host responses at physiological, biological and molecular scales. However, the molecular mechanisms underlying complex begomovirus-whitefly interactions that consequently substantiate efficient virus transmission largely remain unknown. Previously, we found that whitefly Asia II 7 cryptic species can efficiently transmit (CLCuMuV) while MEAM1 cryptic species is a poor carrier and incompetent vector of CLCuMuV. To investigate the potential mechanism/s that facilitate the higher acquisition of CLCuMuV by its whitefly vector (Asia II 7) and to identify novel whitefly proteins that putatively interact with CLCuMuV-AV1 (coat protein), we employed yeast two-hybrid system, bioinformatics, bimolecular fluorescence complementation, RNA interference, RT-qPCR and bioassays. We identified a total of 21 Asia II 7 proteins putatively interacting with CLCuMuV-AV1. Further analyses by molecular docking, Y2H and BiFC experiments validated the interaction between a whitefly innate immunity-related protein (BTB/POZ) and viral AV1 (coat protein). Gene transcription analysis showed that the viral infection significantly suppressed the transcription of / and enhanced the accumulation of CLCuMuV in Asia II 7, but not in MEAM1 cryptic species. In contrast to MEAM1, the targeted knock-down of / substantially reduced the ability of Asia II 7 to acquire and accumulate CLCuMuV. Additionally, antiviral immune signaling pathways ( , , and / ) were significantly suppressed following viral infection of Asia II 7 whiteflies. Taken together, the begomovirus CLCuMuV potentiates efficient virus accumulation in its vector Asia II 7 by targeting and suppressing the transcription of an innate immunity-related / gene and other antiviral immune responses in a cryptic species-specific manner.