Research Article: Continuous Influx of Genetic Material from Host to Virus Populations

Date Published: February 1, 2016

Publisher: Public Library of Science

Author(s): Clément Gilbert, Jean Peccoud, Aurélien Chateigner, Bouziane Moumen, Richard Cordaux, Elisabeth A. Herniou, Harmit S. Malik

Abstract: 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.

Partial Text: The genomes of large eukaryotic double-stranded DNA viruses contain high proportions of cellular genes resulting from host-to-virus horizontal transfers (HT) [1–4]. For example, at least 10% of giant virus genes and up to 30% of herpesvirus genes likely originated from eukaryote or prokaryote genomes [1, 5, 6]. Some of these genes have been shown to act as key factors in the etiology of viral diseases [7, 8]. Because cellular gene content can be quite different between closely related viruses and/or quite similar between distantly related viruses [1, 2, 9], viral co-option of host genes appears to be rather frequent during virus evolution. The cellular genes that have so far been identified in viral genomes result from relatively ancient host-to-virus HT events. From a population genetics perspective, these viral-borne host genes must have been inherited at low to intermediate frequencies over multiple rounds of viral replication until they finally reached fixation in the viral species, likely because they provided a fitness gain to the virus. In agreement with this hypothesis, many of these genes are thought to play a role in thwarting host anti-viral defenses, thus facilitating viral replication [10]. A corollary of this scenario is that many viral-borne host genes resulting from host-to-virus HT should be found at varying frequencies in viral populations. However, host-to-virus HT has never been investigated at the micro-evolutionary scale of the viral population. Therefore, the frequency of host-to-virus HT as well as the evolutionary and molecular processes underlying the capture and domestication of eukaryotic genes by viruses remain poorly understood.