MAPP · Mosquito Antiviral piRNA Pathway

Mosquito Antiviral piRNA Pathway

Chikungunya virus (CHIKV, genus Alpahvirus) and Zika virus (ZIKV, genus Flavivirus) belong to a group of viruses that are transmitted by Aedes aegypti mosquitoes and cause severe disease in humans including fever, headache, malaise, arthritis and in the case of ZIKV neurological disease and birth defects. Mosquito-transmitted viruses put a huge economical and medical burden on societies in high risk areas. The epidemic spread of chikungunya virus began approximately 10 years ago, in the Indian Ocean region and later reached Europe (France and Italy). In recent years, the disease reached South America and USA. The Zika virus epidemic began later, at the beginning of 2015 in Brazil and has now spread across South America. Mosquitoes are not just the carrier but also become infected with the virus which spreads through the whole organism. Their immune system actively fights the virus; however, mosquitos do not have an antibody based immune system and yet the infection is asymptomatic and not pathogenic. In case of the human host, the activation of the adaptive immune system (e.g. antibodies, T-cells) is required to clear the organism of virus infection. On the other hand, mosquitoes have an efficient innate immune system that acts on the cellular level to control the virus replication but is unable to clear the virus from the organism. This persistent infection of the mosquito is thought to be important factor for an efficient viral transmission to humans. The main antiviral response in mosquitoes is based on virus specific small RNA molecules (and their key interacting proteins) that are used to identify and silence the replicating virus. Over the years many studies have identified different classes of virus-specific small RNAs in infected mosquito cells, called small interfering (si)RNAs, micro (mi)RNAs and PIWI-interacting (pi)RNAs. Recent findings have suggested that the piRNAs (and the interacting key proteins: Piwi1-7 and Ago3), in addition to the rather well characterized siRNAs (and key proteins: Ago2 and Dcr2), have antiviral potential in mosquitoes. The aim of the project was to characterize if and how piRNAs are antiviral against mosquito-borne viruses in their main mosquito vector, Aedes aegypti: (i) dissecting the role of the piRNA pathway as antiviral response against CHIKV and ZIKV, (ii) identification of the piRNA pathway proteome and bound RNAs in Aedes aegypti and their changes during CHIKV and ZIKV, (iii) the role of novel piRNA related proteins in the antiviral response against CHIKV and ZIKV. During the project it was found that although CHIKV and ZIKV infection results in the production of virus-specific piRNAs, these do not carry antiviral protective role. Only antiviral PIWI proteins was found to be Piw4, yet it does not bind piRNAs itself and is not involved in their production. Piwi4 also binds multiple other cellular protein, some of these are also antiviral.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз