Many genes of large double-stranded DNA viruses have a cellular origin, suggesting that host-to-virus horizontal transfer (HT) of DNA is recurrent. Yet, the frequency of these transfers has never been assessed in viral populations. Here we used ultra-deep DNA sequencing of 21 baculovirus populations extracted from two moth species to show that a large diversity of moth DNA sequences (n = 86) can integrate into viral genomes during the course of a viral infection. The majority of the 86 different moth DNA sequences are transposable elements (TEs, n = 69) belonging to 10 superfamilies of DNA transposons and three superfamilies of retrotransposons. The remaining 17 sequences are moth sequences of unknown nature. In addition to bona fide DNA transposition, we uncover microhomology-mediated recombination as a mechanism explaining integration of moth sequences into viral genomes. Many sequences integrated multiple times at multiple positions along the viral genome. We detected a total of 27,504 insertions of moth sequences in the 21 viral populations and we calculate that on average, 4.8% of viruses harbor at least one moth sequence in these populations. Despite this substantial proportion, no insertion of moth DNA was maintained in any viral population after 10 successive infection cycles. Hence, there is a constant turnover of host DNA inserted into viral genomes each time the virus infects a moth. Finally, we found that at least 21 of the moth TEs integrated into viral genomes underwent repeated horizontal transfers between various insect species, including some lepidopterans susceptible to baculoviruses. Our results identify host DNA influx as a potent source of genetic diversity in viral populations. They also support a role for baculoviruses as vectors of DNA HT between insects, and call for an evaluation of possible gene or TE spread when using viruses as biopesticides or gene delivery vectors. Author Summary While gene exchange is known to occur between viruses and their hosts, this phenomenon has never been studied at the level of the viral population. Here we report that each time a virus from the Baculoviridae family infects a moth, a large number (dozens to hundreds) and high diversity of moth DNA sequences (86 different sequences) can integrate into replicating viral genomes. These findings show that viral populations carry a measurable load of host DNA sequences, further supporting the role of viruses as vectors of horizontal transfer of DNA between insect species. The potential uncontrolled gene spread associated with the use of viruses produced in insect cells as gene delivery vectors and/or biopesticides should therefore be evaluated.
【초록키워드】 viruses, viral infection, Infection, virus, Population, Spread, DNA, Viral, vector, Recombination, gene delivery, viral genomes, genetic diversity, DNA sequencing, Insects, mechanism, baculovirus, cellular, Frequency, integration, viral genome, in addition to, transposable elements, infection cycles, Support, average, sequence, transfer, hosts, insertion, insect cells, DNA sequences, element, retrotransposons, DNA sequence, vectors, baculoviruses, host DNA, moth, while, infect, Host, repeated, susceptible, populations, Course, produced, identify, virus, proportion, addition, evaluated, majority, in viral, occur, insect cell, baculovirus, double-stranded, transposon, Baculoviridae, calculate, DNA virus, 【제목키워드】 Population, material, influx, Continuous,