Infection of the germ line by retroviral particles produced in the follicle cells: a possible mechanism for the mobilization of the gypsy retroelement of Drosophila

Abstract

The gypsy retroelement of Drosophila moves at high frequency in the germ line of the progeny of females carrying a mutation in the flamenco (flam) gene. This high rate of de novo insertion correlates with elevated accumulation of full-length gypsy RNA in the ovaries of these females, as well as the presence of an env-specific RNA. We have prepared monoclonal antibodies against the gypsy Pol and Env products and found that these proteins are expressed in the ovaries of flam females and processed in the manner characteristic of vertebrate retroviruses. The Pol proteins are expressed in both follicle and nurse cells, but they do not accumulate at detectable levels in the oocyte. The Env proteins are expressed exclusively in the follicle cells starting at stage 9 of oogenesis, where they accumulate in the secretory apparatus of the endoplasmic reticulum. They then migrate to the inner side of the cytoplasmic membrane where they assemble into viral particles. These particles can be observed in the perivitelline space starting at stage 10 by immunoelectron microscopy using anti-Env antibodies. We propose a model to explain flamenco-mediated induction of gypsy mobilization that involves the synthesis of gypsy viral particles in the follicle cells, from where they leave and infect the oocyte, thus explaining gypsy insertion into the germ line of the subsequent generation.

Ongoing endeavors to detect mobilization of transposable elements

“…The signal was all disappeared when gypsy -RNAi was introduced to the same animal, verifying its specificity ( 92 ). This system was further used to show that 1) gypsy transposons like a retrovirus are capable of transmitting intercellularly between Drosophila cells grown in the same culture media ( 93 ), in consistent with finding that gypsy mobilization involves production of gypsy viral particles in the follicle cells to infect the oocyte in Drosophila ( 94 ) and that 2) fly driving glial-specific expression of hTDP43, found to be aggregated in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), experiences gypsy -ERV activation, DNA damage and apoptosis in both glia and nearby neurons, hypothesizing the endogenous retrovirus might contribute to TDP-43-mediated neurodegeneration in non-cell-autonomous manner ( 95 ). Since CLEVR strategy can be applicable to other LTR type retrotransposons, it will enable to improve our understanding of transposable mobilization further in various contexts of biology.…”

Rapid evolution and conserved function of the piRNA pathway

“…These endogenous retroviruses can move from cell to cell, or from animal to animal, leading to horizontal transfer. For example, Drosophila gypsy and ZAM elements expressed in the somatic follicle cells of the ovary can infect adjacent germline cells [20,21]. Another subset of retrotransposons lacks LTRs and is classified as long interspersed elements (LINEs) or short interspersed elements (SINEs).…”

Mechanism and regulation of P element transposition

“…Interestingly, piRNA-mediated regulation of transposon alternative splicing does not seem to be exclusive to P elements, as a similar splicing regulation was also shown to modulate the expression of the Gypsy retrovirus-like element [33]. In this case however, the regulation is restricted to the ovarian somatic cells and Gypsy mRNA splicing favours the production of the Envelope protein mRNA [111], leading to the production of infectious particles that can spread into the surrounding tissues, most notably the germline [112,113].…”