AI Article Synopsis
- RNA interference (RNAi) in mosquitoes involves two pathways, piRNA and exo-siRNA, which produce small RNAs that help combat arbovirus infections, particularly Zika virus (ZIKV).
- The exo-siRNA pathway is considered the primary antiviral mechanism, and in Aedes aegypti cells, ZIKV-specific siRNAs were linked to the protein Argonaute 2 (Ago2), although inhibiting Ago2 didn't increase virus replication.
- Additionally, while piRNA-sized small RNAs were found, they didn't show the normal activity associated with piRNAs, and only one PIWI protein (Piwi4) exhibited any significant antiviral effect against ZIKV.
Article Abstract
RNA interference (RNAi) controls arbovirus infections in mosquitoes. Two different RNAi pathways are involved in antiviral responses: the PIWI-interacting RNA (piRNA) and exogenous short interfering RNA (exo-siRNA) pathways, which are characterized by the production of virus-derived small RNAs of 25-29 and 21 nucleotides, respectively. The exo-siRNA pathway is considered to be the key mosquito antiviral response mechanism. In Aedes aegypti-derived cells, Zika virus (ZIKV)-specific siRNAs were produced and loaded into the exo-siRNA pathway effector protein Argonaute 2 (Ago2); although the knockdown of Ago2 did not enhance virus replication. Enhanced ZIKV replication was observed in a Dcr2-knockout cell line suggesting that the exo-siRNA pathway is implicated in the antiviral response. Although ZIKV-specific piRNA-sized small RNAs were detected, these lacked the characteristic piRNA ping-pong signature motif and were bound to Ago3 but not Piwi5 or Piwi6. Silencing of PIWI proteins indicated that the knockdown of Ago3, Piwi5 or Piwi6 did not enhance ZIKV replication and only Piwi4 displayed antiviral activity. We also report that the expression of ZIKV capsid (C) protein amplified the replication of a reporter alphavirus; although, unlike yellow fever virus C protein, it does not inhibit the exo-siRNA pathway. Our findings elucidate ZIKV-mosquito RNAi interactions that are important for understanding its spread.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5667879 | PMC |
| http://dx.doi.org/10.1371/journal.pntd.0006010 | DOI Listing |
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Article Synopsis
- The exogenous small interfering RNA (exo-siRNA) pathway helps Aedes aegypti mosquitoes fight off viruses that can make humans sick.
- This pathway uses small pieces of RNA, called vsiRNAs, that are made from virus RNA, and they help cut up the virus's genetic material so it can't spread.
- Scientists studied parts of a protein called Dcr2 in these mosquitoes, finding that certain areas are really important for making vsiRNAs and fighting off viruses effectively.
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