Autor(es): Maharaj, Payal D.; Widen, Steven G.; Huang, Jing; Wood, Thomas G.; Thangamani, Saravanan

Resumo: Mosquito borne pathogens are transmitted to humans via saliva during blood feeding. Mosquito saliva is a complex concoction of many secretory factors that modulate the feeding foci to enhance pathogen infection and establishment. Multiple salivary proteins/factors have been identified/characterized that enhance pathogen infection. Here, we describe, for the first time, the identification of exogenous microRNAs from mosquito saliva. MicroRNAs are short, 18-24 nucleotide, non-coding RNAs that regulate gene expression, and are generally intracellular. However, circulating miRNAs have been described from serum and saliva of humans. Exogenous miRNAs have not been reported from hematophagous arthropod saliva. We sought to identify miRNAs in the mosquito saliva and their role in Chikungunya virus (CHIKV) infection. Next generation sequencing was utilized to identify 103 exogenous miRNAs in mosquito saliva of which 31 miRNAs were previously unidentified and were designated novel. Several miRNAs that we have identified are expressed only in the CHIKV infected mosquitoes. Five of the saliva miRNAs were tested for their potential to regulated CHIKV infection, and our results demonstrate their functional role in the transmission and establishment of infection during blood feeding on the host. Mosquito saliva contains a complex repertoire of bioactive factors that are secreted into blood feeding site, the skin. Infected mosquitoes transmit pathogens to the host during feeding via saliva. The bioactive factors in mosquito saliva are responsible for modulating host hemostasis, immune defenses and pain/itch responses, and have been implicated to enhance pathogen infection and establishment in the host. In our efforts to identify and characterize salivary immunomodulators that enhance Chikungunya virus (CHIKV) transmission, we have discovered, for the first time, exogenous microRNA in mosquito saliva. MicroRNAs (miRNAs) are short, 18-24 nucleotide, non-coding RNAs that regulate gene expression. Short non-coding RNAs were extracted from the saliva of Chikungunya virus (CHIKV) infected and uninfected Aedes aegypti and Aedes albopictus saliva, and subjected to Illumina next generation sequencing. Bioinformatic analysis revealed the presence of miRNAs in the mosquito saliva. We have also identified several novel miRNAs that are expressed only during CHIKV infection. Though the functional roles of these miRNAs are yet to be established, our in-vitro data from testing 5 miRNAs demonstrate their role in the regulation of CHIKV infection. These miRNAs may play an important role in regulating the establishment of CHIKV infection in the mammalian host during blood feeding.

Palavras-Chave: Mosquitoes; Proteins; Infections; Gene expression; MicroRNAs

Imprenta: Plos Neglected Tropical Diseases, v. 9, n. 1, 2015.

Descritores: Aedes aegypti - Immune response ; Aedes aegypti - Proteins ; Aedes aegypti - RNA ; Aedes aegypti - Virus ; Aedes aegypti - Transmission ; Aedes aegypti - Public health

Data de publicação: 2015

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