Polintons, virophages and transpovirons: a tangled web linking viruses, transposons and immunity

Abstract

Virophages are satellite DNA viruses that depend for their replication on giant viruses of the family Mimiviridae. An evolutionary relationship exists between the virophages and Polintons, large self-synthesizing transposons that are wide spread in the genomes of diverse eukaryotes. Most of the Polintons encode homologs of major and minor icosahedral virus capsid proteins and accordingly are predicted to form virions. Additionally, metagenome analysis has led to the discovery of an expansive family of Polinton-like viruses (PLV) that are more distantly related to bona fide Polintons and virophages. Another group of giant virus parasites includes small, linear, double-stranded DNA elements called transpovirons. Recent in-depth comparative genomic analysis has yielded evidence of the origin of the PLV and the transpovirons from Polintons. Integration of virophage genomes into genomes of both giant viruses and protists has been demonstrated. Furthermore, in an experimental coinfection system that consisted of a protist host, a giant virus and an associated virophage, the virophage integrated into the host genome and, after activation of its expression by a superinfecting giant virus, served as an agent of adaptive immunity. There is a striking analogy between this mechanism and the CRISPR-Cas system of prokaryotic adaptive immunity. Taken together, these findings show that Polintons, PLV, virophages and transpovirons form a dynamic network of integrating mobile genetic elements that contribute to the cellular antivirus defense and host-virus coevolution.

Giant viruses: spore‐like missing links between Rickettsia and mitochondria?

“…50 These share DNA polymerase B with polintons, linear self-replicating eukaryotic trans-posons reminiscent of capsidless viruses, which are probable players in the evolutionary complex involving polintons, phages, giant viruses, and mitochondria. [51][52][53][54][55][56] Analyses of sequences of RNA polymerases independently confirm the phagemitochondria relationships. 57,58 This suggests that the presence of similar polymerases likely reflects phylogenetic relatedness rather than more or less coincidental lateral transfers as could be inferred from the presence of homologs of mitochondrial membrane proteins in genomes of giant viruses.…”

“…This similarity suggests phyletic relationships that are further strengthened by the observation that phages (bacterio‐ and virophages), giant viruses, and mitochondria have similar DNA polymerases belonging to the DNA‐dependent DNA polymerase family B . These share DNA polymerase B with polintons, linear self‐replicating eukaryotic transposons reminiscent of capsidless viruses, which are probable players in the evolutionary complex involving polintons, phages, giant viruses, and mitochondria . Analyses of sequences of RNA polymerases independently confirm the phage–mitochondria relationships .…”

The dual lifestyle of genome‐integrating virophages in protists

“…Finally, mavirus‐mediated immunity displays interesting parallels to CRISPR‐Cas adaptive immunity, as noted by Koonin and Krupovic . In both systems, virus‐derived genome information is incorporated into the host genome to protect against a lytic pathogen.…”

“…This process effectively qualifies as a defense mechanism on a population level, and implies an intriguing altruistic aspect as it is not the infected cell that profits from the reactivated virophage, but its neighbors . Virophage‐mediated protection against giant viruses can even be regarded as a case of adaptive immunity in unicellular eukaryotes, since previous encounters with a pathogen are recorded in the host genome as immunological memory . Notably though, the immunological memory here is of indirect nature, since not the pathogen itself (the giant virus) is remembered, but its antagonist (the virophage).…”

“…It remains to be seen whether MPEs form capsids and whether they are truly autonomous, or have a similar relationship to other viruses as observed for giant DNA viruses and virophages. In the latter case, some MPEs may have beneficial effects on their hosts and could represent domesticated versions of virophages …”