High resolution proteomics of Aedes aegypti salivary glands infected with either dengue, Zika or chikungunya viruses identify new virus specific and broad antiviral factors

Abstract

Arboviruses such as dengue (DENV), Zika (ZIKV) and chikungunya (CHIKV) viruses infect close to half a billion people per year, and are primarily transmitted through Aedes aegypti bites. Infection-induced changes in mosquito salivary glands (SG) influence transmission by inducing antiviral immunity, which restricts virus replication in the vector, and by altering saliva composition, which influences skin infection. Here, we profiled SG proteome responses to DENV serotype 2 (DENV2), ZIKV and CHIKV infections by using high-resolution isobaric-tagged quantitative proteomics. We identified 218 proteins with putative functions in immunity, blood-feeding or related to the cellular machinery. We observed that 58, 27 and 29 proteins were regulated by DENV2, ZIKV and CHIKV infections, respectively. While the regulation patterns were mostly virus-specific, we separately depleted four uncharacterized proteins that were upregulated by all three viral infections to determine their effects on these viral infections. Our study suggests that gamma-interferon responsive lysosomal thiol-like (GILT-like) has an anti-ZIKV effect, adenosine deaminase (ADA) has an anti-CHIKV effect, salivary gland surface protein 1 (SGS1) has a pro-ZIKV effect and salivary gland broad-spectrum antiviral protein (SGBAP) has an antiviral effect against all three viruses. The comprehensive description of SG responses to three global pathogenic viruses and the identification of new restriction factors improves our understanding of the molecular mechanisms influencing transmission.

Aedes aegypti Strain Subjected to Long-Term Exposure to Bacillus thuringiensis svar. israelensis Larvicides Displays an Altered Transcriptional Response to Zika Virus Infection

“…It is important to consider that other tissues can be assessed, such as the midgut which is the first escape barrier for the virus and also the site of action of Bti toxins. It should be considered that although the gene expression can display variations according to the tissue analyzed [ 29 , 47 , 48 , 49 , 50 ], our data demonstrated a trend of repression of some transcripts involved in arbovirus response from IMD, Toll, and JAK-STAT pathways in the head of infected females, which corroborates their increased susceptibility to ZIKV. However, it is important to note that the antiviral response in mosquitoes can be also regulated by other pathways, whose related genes were not assessed in this study [ 51 ].…”

Arbovirus-vector protein interactomics identifies Loquacious as a co-factor for dengue virus replication in Aedes mosquitoes

“…We characterized the interactome of FLAG-tagged NS1 and NS5 in C6/36 cells by FLAG immunoprecipitation, followed by label-free mass spectrometry ( Fig 1D and 1E and S1 Table ). To prevent false-positives due to perturbation of the cellular proteome by DENV non-structural proteins [ 30 ], we used untagged DENV non-structural proteins as a control. NS1 interacted with 55 proteins, including the viral NS2A, NS3, NS4A and NS4B proteins, whereas NS5 interacted with 45 proteins, including NS1, NS2A, NS3 and NS4A, and a total of 15 host proteins interacted with both NS1 and NS5 (Figs 1D, 1E and 2A and S1 Table ).…”

A Review of Omics Studies on Arboviruses: Alphavirus, Orthobunyavirus and Phlebovirus

“…The SGBAP had an antiviral potential against all three viruses by inhibiting viral propagation. However, its mechanisms remain to be discovered through homily investigation [ 95 ].…”