Virophages are a new discovery in the world of viruses. Unlike conventional viruses that target cellular organisms, virophages infect other viruses. This parasitic relationship reveals a complex layer of interaction within the microscopic world, where even viruses can fall prey to smaller viral entities. Their existence has opened new avenues for understanding viral ecology and evolution.
What Are Virophages?
Virophages are small, double-stranded DNA viruses, measuring 40 to 80 nanometers in length. Their genetic material, which can be circular or linear, ranges from 17 to 30 kilobase pairs (kbp) in size, encased within an icosahedral capsid. These characteristics contrast with their hosts, known as giant viruses, which can have genomes as large as 1 to 2 megabase pairs (Mbp).
Virophages are dependent on these larger viruses for their replication. They require a coinfection with a giant virus, such as Mimiviruses or Pandoraviruses, which infect single-celled eukaryotes like amoebae or algae.
The first virophage, Sputnik, was discovered in 2008 in a cooling tower in Paris, alongside its giant virus host, Acanthamoeba castellanii mamavirus (ACMV). Sputnik relied on ACMV’s replication machinery, and it inhibited ACMV’s replication while improving the survival of the host amoeba.
How Virophages Replicate
Virophages employ a unique replication strategy that highlights their parasitic nature. Their replication cycle begins when they coinfect a host cell alongside a giant virus. Once inside the host cell, the giant virus establishes a specialized compartment called a “viral factory” in the cytoplasm.
The virophage then hijacks this viral factory, taking over the giant virus’s resources and machinery. Virophages utilize the giant virus’s transcriptional and replication mechanisms, including its enzymes and even some of its genetic material, to produce their own viral particles. Without the giant virus’s active replication within the host cell, the virophage cannot multiply.
This dependency means virophages exhibit “parasitism within parasitism.” This interference leads to a reduction in the giant virus’s replication efficiency and can result in the formation of defective giant virus particles. For instance, Sputnik’s coinfection with ACMV can reduce ACMV’s replication efficiency by up to 70%, which in turn helps protect the amoeba host.
Virophages in the Environment
Virophages are widespread in diverse natural environments. They have been identified in marine ecosystems, freshwater bodies, thermal waters, deep-sea vents, and even in soil. Their presence has also been noted in plants, and in animals, including ruminants.
Their ecological role influences viral populations, particularly by weakening giant viruses. This parasitic effect on giant viruses can affect the dynamics of microbial communities. For example, in aquatic environments, virophages can help regulate algal blooms by suppressing the giant viruses that infect algae.
The integration of virophage genomes into the genomes of single-celled eukaryotes is observed, where they can reactivate upon giant virus infection. This integration provides a form of inducible antiviral defense for the eukaryotic host, potentially improving the host’s recovery and survival from giant virus infections. The widespread presence and dynamic integration of virophages suggest their ongoing and significant contribution to microbial interactions and nutrient cycling within ecosystems.
Potential Uses of Virophages
The unique parasitic relationship of virophages with giant viruses suggests several promising applications in various fields. One area is their potential as biocontrol agents against harmful giant viruses. For example, virophages could be used to manage or prevent algal blooms caused by giant viruses that infect algae, helping to maintain ecosystem balance.
Beyond environmental control, virophages are being explored as novel antiviral agents. Their ability to interfere with the replication of giant viruses makes them candidates for combating giant viruses that might pose threats to other organisms, including human or animal health. Scientists are investigating if virophages could be engineered to target specific giant viruses associated with diseases.
Research is also considering the possibility of using genetically modified virophages as vectors for vaccine antigens or as tools in biotechnology. While still in early stages, the concept of synthetic virophage biosynthesis offers a hypothetical path for addressing viral challenges, including against viruses like SARS-CoV-2, by engineering virophages to disrupt their replication without harming the host.