TWiV 139: Honey, I shrunk the virus

mimivirusHosts: Vincent Racaniello, Alan Dove, and Dickson Despommier

Vincent, Alan, and Dickson discuss the reduction in genome size of Mimivirus upon passage in amoeba, and analysis of the microbiome of honeybees.

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Alan – Life Before the Dinosaurs by ABC
Dickson – Inside Jokes by Matthew M. Hurley
Vincent – The Tree of Life by Jonathan Eisen

Listener Pick of the Week

Lance – A History of the World since 9/11 by Dominic Streatfeild

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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 93: Our infectious inbox

Hosts: Vincent Racaniello, Alan Dove, and Rich Condit

On episode #93 of the podcast This Week in Virology, Vincent, Alan, and Rich answer listener questions about lab procedures, prokaryotes, endogenous retroviruses, the iPad and teaching, prions, mimivirus, splitting water with viruses, and the polio outbreak in Tajikistan.

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Alan – Southern Fried Science
Rich –
Tree of Life web project
Vincent – Dickson Despommier at Big Think

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The virus and the virion

The illustration at left depicts a virion – the infectious particle that is designed for transmission of the nucleic acid genome among hosts or host cells. A virion is not the same as a virus. I define virus as a distinct biological entity with five different characteristics. Others believe that the virus is actually the infected host cell.

The idea that virus and virion are distinct was first proposed by Bandea in 1983. He suggested that a virus is an organism without a cohesive morphological structure, with subsystems that are not in structural continuity:

Viruses are presented as organisms which pass in their ontogenetic cycle through two distinctive phenotypic phases: (1) the vegetative phase and (2) the phase of viral particle or nucleic acid. In the vegetative phase, considered herein to be the ontogenetically mature phase of viruses, their component molecules are dispersed within the host cell. In this phase the virus shows the major physiological properties of other organisms: metabolism, growth, and reproduction.

According to Bandea’s hypothesis, the infected cell is the virus, while the virus particles are ‘spores’ or reproductive forms. His theory was largely ignored until the discovery of the giant mimivirus, which replicates its DNA genome and produces new virions in the cytoplasm within complex viral ‘factories’. Claverie suggested that the viral factory corresponds to the organism, whereas the virion is used to spread from cell to cell. He wrote that “to confuse the virion with the virus would be the same as to confuse a sperm cell with a human being”.

If we accept that the virus is the infected cell, then it becomes clear that most virologists have confused the virion and the virus. This is probably a consequence of the fact that modern virology is rooted in the study of bacteriophages that began in the 1940s. These viruses do not induce cellular factories, and disappear (the eclipse phase) early after cell entry. Contemporary examples of such confusion include the production by structural virologists of virus crystals, and the observation that viruses are the most abundant entities in the seas. In both cases it is the virion that is being studied. But virologists are not the only ones at fault – the media writes about the AIDS virus while showing an illustration of the virion.

Those who consider the virus to be the infected cell also believe that viruses are alive.

…one can conclude that infected eukaryotic cells in which viral factories have taken control of the cellular machinery became viruses themselves, the viral factory being in that case the equivalent of the nucleus. By adopting this viewpoint, one should finally consider viruses as cellular organisms. They are of course a particular form of cellular organism, since they do not encode their own ribosomes and cell membranes, but borrow those from the cells in which they live.

This argument leads to the assumption that viruses are living, according to the classical definition of living organisms as cellular organisms. Raoult and Forterre have therefore proposed that the living world should be divided into two major groups of organisms, those that encode ribosomes (archaea, bacteria and eukarya), and capsid-encoding organisms (the viruses).

BANDEA, C. (1983). A new theory on the origin and the nature of viruses Journal of Theoretical Biology, 105 (4), 591-602 DOI: 10.1016/0022-5193(83)90221-7

Forterre, P. (2010). Defining Life: The Virus Viewpoint Origins of Life and Evolution of Biospheres, 40 (2), 151-160 DOI: 10.1007/s11084-010-9194-1

TWiV 77: Non-nuclear proliferation

Hosts: Vincent Racaniello, Alan Dove, and Rich Condit

Vincent, Alan, and Rich revisit circovirus contamination of Rotarix, then discuss poxvirus-like replication of mimivirus in the cell cytoplasm, and whether seasonal influenza immunization increases the risk of infection with the 2009 H1N1 pandemic virus.

This episode is sponsored by Data Robotics Inc. Use the promotion code TWIVPOD to receive $50 off a Drobo or $100 off a Drobo S.

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Rich The Way We Work by David Macaulay
Alan DimDim
Vincent Polio: An American Story by David Oshinsky

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TWiV 63: Melting pot virus

marseillevirus_genomeHosts: Vincent Racaniello, Alan Dove, and Rich Condit

On episode 63 of the podcast This Week in Virology, Vincent, Alan, and Rich talk about US government contract for freeze-dried smallpox vaccine, red squirrels in the UK threatened by poxvirus, and Marseillevirus, another DNA virus from amoebae built for comfort and speed.

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Rich Infectious Awearables
Alan Darwine
Vincent Microbial Art

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TWiV 32: Influenza in silico

twiv-200On episode #32 of the podcast “This Week in Virology”, Vincent, Alan, and Raul Rabadan converse about polio survivors in iron lungs, bocavirus, structure of mimivirus, and genome sequence analysis of influenza H1N1 viruses.

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