TWiV 206: Viral turducken

On episode #206 of the science show This Week in Virology, Vincent, Alan, Dickson, and Kathy discuss how the innate immune response to viral infection influences the production of pluripotent stem cells, and the diverse mobilome of giant viruses.

You can find TWiV #206 at www.microbe.tv/twiv.

Brent Johnson on virophage

Virophage is the name coined for viruses such as Sputnik and Mavirus that can only replicate in cells infected with a helper virus, whose replication they inhibit. I’ve never liked the name – it means virus eater – and neither does Brent Johnson, a virologist at Brigham Young University:

“I believe the term ‘virophage’ is unfortunate because it implies one virus is infecting another virus and eating it. The small virus isn’t infecting another virus, it’s just using it to assist in replication, which is consistent with the needs of a defective virus.” he explains. He prefers calling the giant viruses “megaviruses,” and considers the name “Megavirus-Associated Virus (MAV) more consistent with currently accepted virus nomenclature.”

For more discussion, see the article by Marsha Stone in the July 2011 Microbe.

TWiV 128: Virologists in the mist

gorillaHosts: Vincent Racaniello, Alan Dove, Dickson Despommier, and Welkin Johnson

Vincent, Alan, Dickson and Welkin review how a virus regulates the severity of mucocutaneous leishmaniasis, virophage control of antarctic algal host-virus dynamics, and human metapneumovirus infection in gorillas.

Click the arrow above to play, or right-click to download TWiV #128 (67 MB .mp3, 92 minutes).

Subscribe to TWiV (free) in iTunes , at the Zune Marketplace, by the RSS feed, by email, or listen on your mobile device with the Microbeworld app.

Links for this episode:

Weekly Science Picks

Welkin – Walter Reed Collection, University of Virginia
Dickson – Bacteria-phage antagonistic coevolution in soil (Science)
Alan –
The Artful Amoeba
Vincent – Potential bacteriophage applications (Microbe)

Send your virology questions and comments (email or mp3 file) to twiv@microbe.tv, or call them in to 908-312-0760. You can also post articles that you would like us to discuss at microbeworld.org and tag them with twiv.

Virophages engineer the ecosystem

organic lake virophageLast week we discussed the second known virophage, but we didn’t have any explanation of why such viruses might evolve. This week we have the discovery of a third virophage, hints of many more, and a hypothesis for what they might be doing in the global ecosystem.

The newest virus eater is called Organic Lake virophage (OLV), for the body of water in Antarctica where it was identified. Antarctic Lakes are well suited for metagenomic analyses (nucleotide sequences produced from environmental samples) because they are dominated by microbes and typically sustain few multicellular eukaryotes. For example, a metagenomic study of Lake Limnopolar, another Antarctic lake, revealed many novel eukaryotic and ssDNA viruses.Nucleotide sequence analysis of water samples taken from Organic Lake in 2006 and 2008 revealed the presence of three abundant phycodnaviruses. These are large, dsDNA-containing viruses that infect algae. Among the sequences was a novel virophage, called Organic Lake virophage (OLV), related to Sputnik virophage, but with a larger circular dsDNA genome (26,421 bp, pictured). OLV was found in water samples taken two years apart, indicating that it is a stable part of the Organic Lake ecosystem.

Because phycodnaviruses are related to mimivirus, it is assumed that OLV replicates in phycodnavirus-infected cells and inhibits the viral production. However, an experiment to test this relationship was not done. Six of the OLV genes are related to genes found in the lake phycodnaviruses, suggesting that gene exchange between virus and virophage has occurred, likely during co-infection of the same host.

When the Sputnik virophage infects mimivirus-infected amoebae, the yield of the larger virus is decreased by 70%, and there is also a threefold inhibition of virus-induced cell lysis. The authors speculated that the Organic Lake virophage could therefore influence the composition of the microbial community. To test this idea, they conducted mathematical modeling of the effect of virophage on a population of microbes that is infected with a lytic virus. Without the virophage, there are cycles of virus reproduction, cell death, and cell growth (blooms). The effect of adding OLV to the equation is that the frequency of blooms increases. The authors suggest that the virophage has this effect by reducing mortality of the host algal cell caused by phycodnaviruses. Antarctic lakes have long cycles of daylight and darkness, and a decrease in phycodnavirus cell killing caused by virophages may be essential for maintaining stability of the microbial food web.

This hypothesis makes perfect sense, and would explain why virophages evolved, but it is based in part on data on how Sputnik virophage interferes with mimivirus. It will be necessary to confirm that OLV indeed inhibits the replication of phycodnaviruses. Furthermore, proving that OLV affects microbial communities in lakes will require extensive field studies.

Perhaps even more interesting than the notion that virophages may engineer ecosystems is finding them in a broader range of environments. Virophage sequences were found in water samples from nearby Ace Lake, and a search of the Global Ocean Survey database revealed virophage sequences in a hypersaline lagoon and an ocean upwelling in the Galapagos islands, a Delaware Bay estuary in New Jersey, and a freshwater lake in Panama.

It is well known that cell killing by viruses has a major impact on ocean ecology. By regulating virus-induced cell lysis, virophages might also have a major effect on aquatic ecology. This possibility makes me wonder if there are virophages of animal viruses that might regulate viral pathogenesis.

Yau S, Lauro FM, Demaere MZ, Brown MV, Thomas T, Raftery MJ, Andrews-Pfannkoch C, Lewis M, Hoffman JM, Gibson JA, & Cavicchioli R (2011). Virophage control of antarctic algal host-virus dynamics. Proceedings of the National Academy of Sciences of the United States of America PMID: 21444812

Virophage, the virus eater

mavirusA second virophage has been identified. The name does not signify a virus that infects another virus – it means virus eater.

The story of virophages begins with the giant mimivirus, originally isolated from a cooling tower in the United Kingdom. It is the largest known virus, with a capsid 750 nanometers in diameter and a double-stranded DNA genome 1.2 million base pairs in length. If these statistics are not sufficiently impressive, consider that shortly after its discovery, an even larger related virus was discovered and called mamavirus. These huge viruses replicate in amoeba such as Acanthamoeba; in this host they form large, cytoplasmic ‘factories’ where the DNA replicates and new virions are assembled. While examining mamavirus infected Acanthamoeba polyphaga, investigators noted small icosahedral virions, 50 nm in diameter, within factories and in the cell cytoplasm. They called this smaller virus Sputnik. This new virus does not replicate in amoebae unless the cell is also infected with mimivirus or mamavirus. Surprisingly, infection with Sputnik reduces the yields of mamavirus, and also decreases the extent of amoebal killing by the larger virus.

The second virophage is called Mavirus (for Maverick virus – because the viral DNA is similar to the eponymous DNA transposon). Mavirus was identified in the marine phagotropic flagellate Cafeteria roenbergensis infected with – you guessed it – a giant virus, CroV.  Like Sputnik, Mavirus cannot replicate in C. roenbergensis without CroV, and it also reduces the yield of CroV particles produced. The figure shows a viral factory (VF) in C. roenbergensis surrounded by large CroV particles (white arrowhead) and the smaller Mavirus particles (white arrows).

There are other examples of viruses that depend on a second, different virus for replication. For example, satellites are small, single-stranded RNA molecules 500-2000 nucleotides in length that replicate only in the presence of a helper virus. The satellite genome typically encodes structural proteins that encapsidate the genome; replication functions are provided by the helper. Most satellites are associated with plant viruses, and cause distinct disease symptoms compared with those caused by helper virus alone. Some bacteriophages and animal viruses have satellites. E. coli bacteriophage T4 is a satellite that requires bacteriophage T2 as a helper, while the adeno-associated viruses within the Parvoviridae are satellites requiring adenovirus or herpesvirus helpers. The hepatitis delta virus genome is a 1.7 kb RNA molecule that requires co-infection with hepatitis B virus to provide capsid proteins.

The difference between Sputnik, Mavirus, and satellites is that the latter do not interfere with the replication of helper viruses. Indeed, Sputnik was termed a virophage by its discoverers because its presence impairs the reproduction of another virus. The name is derived from bacteriophage – the name means ‘bacteria eater’ (from the Greek phagein, to eat). The idea is that one virus impairs the replication of the other – ‘eating’ the other virus.

In addition to their unique effect on their helper viruses, it appears that virophages have other stories to tell. The Sputnik DNA genome contains genes related to those in viruses that infect eukaryotes, prokaryotes, and archaea. Virophages may therefore function to transfer genes among viruses. The relationship of Mavirus to DNA transposons is also intriguing. DNA transposons are a kind of ‘jumping gene’, a piece of DNA that can move within and between organisms. They are important because they can change the genetic makeup of living entities, thereby influencing evolution. It is possible that DNA transposons evolved from ancient relatives of Mavirus, which would give virophages a particularly important role in the evolution of eukaryotes.

Fischer MG, & Suttle CA (2011). A Virophage at the Origin of Large DNA Transposons. Science (New York, N.Y.) PMID: 21385722

TWiV 125 – TWiV infects FiB

icosahedron light

Hosts: Vincent Racaniello, Dickson DespommierAlan DoveRich Condit, and Marc Pelletier

This Week in Virology and Futures in Biotech join together in a science mashup to talk about a virophage at the origin of DNA transposons, and unintended spread of a recombinant retrovirus.

Click the arrow above to play, or right-click to download TWiV #125 (59 MB .mp3, 81 minutes).

Subscribe to TWiV (free) in iTunes , at the Zune Marketplace, by the RSS feed, by email, or listen on your mobile device with the Microbeworld app.

Links for this episode:

Weekly Science Picks

Marc – JotNot
Dickson – New bunyavirus in China (NEJM)
Rich – Listening to the Deep Ocean Environment (LIDO) recording of the Hatsushima earthquake (ScienceDaily article) – thanks Bridget!
Alan –Walter and Ina: A Story of Love, War, and Science
Vincent – Icosahedral light fixture (thanks, Eric!)

Send your virology questions and comments (email or mp3 file) to twiv@microbe.tv, or call them in to 908-312-0760. You can also post articles that you would like us to discuss at microbeworld.org and tag them with twiv.