Endogenous non-retroviral elements in genomes of Aedes mosquitoes and vector competence

Abstract

Recent extensive (re)emergences of arthropod-borne viruses (arboviruses) such as chikungunya (CHIKV), zika (ZIKV) and dengue (DENV) viruses highlight the role of the epidemic vectors, Aedes aegypti and Aedes albopictus, in their spreading. Differences of vector competence to arboviruses highlight different virus/vector interactions. While both are highly competent to transmit CHIKV (Alphavirus,Togaviridae), only Ae. albopictus is considered as a secondary vector for DENV (Flavivirus, Flaviviridae). Among other factors such as environmental temperature, mosquito antiviral immunity and microbiota, the presence of non-retroviral integrated RNA virus sequences (NIRVS) in both mosquito genomes may modulate the vector competence. Here we review the current knowledge on these elements, highlighting the mechanisms by which they are produced and endogenized into Aedes genomes. Additionally, we describe their involvement in antiviral immunity as a stimulator of the RNA interference pathways and in some rare cases, as producer of viral-interfering proteins. Finally, we mention NIRVS as a tool for understanding virus/vector co-evolution. The recent discovery of endogenized elements shows that virus/vector interactions are more dynamic than previously thought, and genetic markers such as NIRVS could be one of the potential targets to reduce arbovirus transmission.

Keywords: NIRVS; arboviral diseases; vector competence.

Figure 1.

World distribution of Aedes albopictus and Aedes aegypti.

Figure 2.

Formation and antiviral functions of NIRVS. When a non-retroviral virus infects a cell, the viral RNA is released and double stranded RNA (dsRNA) intermediates are produced. Viral dsRNA is then used as a template to produce viral DNA (vDNA) by the reverse transcriptase activity of retrotransposon elements (1). vDNA integrates into the host cell genome, probably by transposition activity of retrotransposons, becoming a NIRVS (2). NIRVS is then transcribed either into siRNAs or piRNAs (3) to inhibit the viral RNA after association with the RISC complex (4) or into mRNA (5), and translated into a dominant negative form protein (6), that can alter the viral replication by several ways. For example, by inhibiting the viral replication complex (7) or viral assembly (8).