Amoebae, Giant Viruses, and Virophages Make Up a Complex, Multilayered Threesome

Abstract

Viral infection had not been observed for amoebae, until the Acanthamoeba polyphaga mimivirus (APMV) was discovered in 2003. APMV belongs to the nucleocytoplasmatic large DNA virus (NCLDV) family and infects not only A. polyphaga, but also other professional phagocytes. Here, we review the Megavirales to give an overview of the current members of the Mimi- and Marseilleviridae families and their structural features during amoebal infection. We summarize the different steps of their infection cycle in A. polyphaga and Acanthamoeba castellani. Furthermore, we dive into the emerging field of virophages, which parasitize upon viral factories of the Megavirales family. The discovery of virophages in 2008 and research in recent years revealed an increasingly complex network of interactions between cell, giant virus, and virophage. Virophages seem to be highly abundant in the environment and occupy the same niches as the Mimiviridae and their hosts. Establishment of metagenomic and co-culture approaches rapidly increased the number of detected virophages over the recent years. Genetic interaction of cell and virophage might constitute a potent defense machinery against giant viruses and seems to be important for survival of the infected cell during mimivirus infections. Nonetheless, the molecular events during co-infection and the interactions of cell, giant virus, and virophage have not been elucidated, yet. However, the genetic interactions of these three, suggest an intricate, multilayered network during amoebal (co-)infections. Understanding these interactions could elucidate molecular events essential for proper viral factory activity and could implicate new ways of treating viruses that form viral factories.

Keywords: Acanthamoeba polyphaga mimivirus (APMV); mimivirus; nucleocytoplasmatic large DNA virus (NCLDV); pathogen defense; virophage.

Figure 1

Structure of APMV and the core genes and relationship of giant viruses. (A) Viral particles of APMV feature a viral core with the genome, mRNAs, and prefabricated proteins. This core is surrounded by the indicated membranes and the capsid structure that contains a pentagonal, star-shaped structure termed “stargate,” which is involved in the release of the viral core into the host cell's cytosol upon phagocytosis. The capsid is decorated with a compact layer of fibrils. For details see main text. (B) Cladogram displaying the relationships of the different lineages of the Mimiviridae and Marseilleviridae. Since the discovery of APMV, over 100 new mimivirus strains have been characterized using samples of various origins in amoebal co-culture methods (Pagnier et al., ; Khalil et al., 2016a,b). All Mimiviridae share a capsid size between 370 and 600 nm and a 1.02–1.26 Mb AT-rich genome which encodes about 1.000 putative proteins (Colson et al., 2017). Based on sequence homology, the Mimiviridae can be divided into three distinct lineages: lineage A with APMV as prototype and a total of 18 members, as reviewed recently (Colson et al., 2017), lineage B with the moumouvirus as prototype and four additional members (Yoosuf et al., ; Colson et al., 2017), and lineage C with Megavirus chiliensis as prototype and a total of 12 members (Arslan et al., ; Colson et al., 2017). The tree was created using the sequences of the D13 major capsid proteins of the indicated prototype viruses using Phylogeny.fr, with the relative evolutionary distance indicated (Dereeper et al., 2008, 2010). (C) List of nine genes conserved throughout all NCLDV families.