Viruses are small DNA- or RNA-based infectious agents that can replicate only inside living cells of a host organism. Most people know what a virus is, and many of us harbor at least one or two of them at some point during the cold and flu season. However, I would guess that many of us do not know what a virophage is, even though they seem to be more common than previously thought.
Virophages were first discovered and characterized by LaScola et al. in 2008 (1) during studies with Acanthamoeba polyphaga mimivirus (APMV), the largest known virus—so large that it is visible by optical microscopy. These researchers were studying a new, larger strain of APMV, which they detected using transmission electron microscopy of A. polyphaga cells inoculated with water from a cooling tower in Paris and dubbed “mamavirus”. In addition to mamavirus particles, they noticed small icosahedral particles approximately 50nm in diameter associated with the mamavirus replication machinery and in the cytoplasm of infected cells. LaScola and his team quickly determined that these particles could not replicate when inoculated into cultures of Acanthamoeba alone but could replicate when co-inoculated with mimivirus or mamavirus. While these particles seemed similar to satellite viruses, which also rely on both a host cell and a second (helper) virus for replication, they differed in that they interfered with replication of the second virus. Co-infection of Acanthamoeba with mamavirus and this new particle resulted in increased formation of abnormal mamavirus virions, a ~70% decrease in the number of infectious mamavirus particles and a threefold decrease in host cell lysis after 24 hours. Borrowing from the word “bacteriophage”, they coined the term virophage to describe this new type of virus, which is more parasitic than symbiotic. They named this particular virophage Sputnik.
Researchers recently discovered virophages similar to Sputnik in East Antarctica in Organic Lake, a shallow eutrophic hypersaline lake with a high concentration of dimethylsulphide (2). This harsh ecosystem is dominated by microbes, and accompanying these microbes are viruses, which are known to greatly affect microbial population levels and nutrition cycling by infecting and lysing host cells. To identify the microscopic residents of Organic Lake, Yau et al. collected surface water, isolated the organisms by filtration and performed shotgun sequencing to generate the Organic Lake metagenome. Within this collective genome, they identified a virophage related to Sputnik integrated into the genome of Organic Lake phycodnaviruses (OLPV), viruses that infect phototrophic algae.
The researchers sequenced the entire genome of the Organic Lake virophage (OLV) and identified 25 putative protein-coding regions, some of which have homologs in Sputnik (27–42% identity at the amino acid level), including a major capsid protein. To identify other potential virophages, the researchers searched sequence data generated as part of the Global Ocean Sampling expedition, looking for sequences similar to the OLV major capsid protein-coding region. They found homologous sequences in a variety of aquatic systems, including another antarctic lake (Ace Lake), a hypersaline lagoon and ocean upwelling site in the Galapagos Islands, an estuary in New Jersey and a fresh water lake in Panama. Obviously, this class of organisms, if we can call a virophage an organism, is not unique to antarctic lakes.
Interestingly, the researchers also identified a 7,408bp region of the OLV genome that encodes six proteins that are more closely related to phycodnavirus proteins (32–65% identity) than to Sputnik proteins, implying an exchange of genetic material between the virus and virophage and possible co-evolution. This implication is supported by the observation that Sputnik and mamavirus also share four homologous genes. Such exchange suggests an indirect mechanism of gene transfer between giant viruses.
Remembering the adverse effects of Sputnik on mamavirus replication, Yau et al. decided to simulate the effects of OLV infection on host algal cell and phycodnavirus populations. Their models of population dynamics predicted a dramatic virophage-mediated decrease in host cell mortality and an increased frequency of algal blooms during the summer months. The researchers hypothesized that the decreases in OLPV virulence and host cell mortality influence carbon flux and are instrumental in stabilizing the microbial food web in Organic Lake and other similar ecosystems.
Thus, something as small as a virophage can have a huge effect. These tiny particles are forcing scientists to rethink the dynamics of host-virus relationships. Of course, one can imagine evolutionary pressure for host cells to cultivate virophages to protect themselves from infection by giant viruses. In fact, there may be evidence to support this. Recently, other researchers studying the Mavirus virophage, which preys on the giant Cafeteria roenbergensis virus, discovered homology between this virophage and eukaryotic DNA transposons, which are also known as “jumping genes” due to their ability to move to new positions within a cellular genome (3). Based on this genetic similarity, modern DNA transposons may be the genetic remnants of protective DNA virophages.
- LaScola, B. et al. (2008) The virophage as a unique parasite of the giant mimivirus. Nature 455, 100–104.
- Yau, S. et al. (2011). Virophage control of antarctic algal host-virus dynamics. Proc. Natl. Acad. Sci. USA PMID: 21444812
- Fischer, M.G. et al. (2011) A virophage at the origin of large DNA transposons. Science PMID:21385722
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