University of Nebraska - Lincoln DigitalCommons@University of Nebraska - Lincoln James Van Etten Publications Plant Pathology Department 2011 Giant Viruses James L. Van Etten University of Nebraska - Lincoln, [email protected] Follow this and additional works at: https://digitalcommons.unl.edu/vanetten Part of the Genetics and Genomics Commons, Plant Pathology Commons, and the Viruses Commons Van Etten, James L., "Giant Viruses" (2011). James Van Etten Publications. 4. https://digitalcommons.unl.edu/vanetten/4 This Article is brought to you for free and open access by the Plant Pathology Department at DigitalCommons@University of Nebraska - Lincoln. It has been accepted for inclusion in James Van Etten Publications by an authorized administrator of DigitalCommons@University of Nebraska - Lincoln. FEATURE ARTICLE — American Scientist 99:4 (July-August 2011), pp. 304-311. Giant Viruses The recent discovery of really, really big viruses is changing views about the nature of viruses and the history of life James L. Van Etten James L. Van Etten is William Altington Distinguished Professor of Plant Pathology at the University of Nebraska–Lincoln. He received his Ph.D. in plant pathology from the University of Illinois, Urbana. He was elected a member of the National Academy of Sciences in 2003 and was a recipi- ent of the Nebraska Sigma Xi Outstanding Scientist Award in 1999. he common view of viruses, mostly ing Poxviridae, which infects vertebrates for isolating virus particles is filtration Ttrue, is of tiny burglars that sneak (for example, smallpox virus) and inver- through filters with pores of 200 nano- into cells, grab the biosynthetic controls tebrates, the aquatic viruses Iridoviridae meters. With viruses all but defined as and compel the cell to make huge num- and Phycodnaviridae, and the vertebrate replicating particles that occur in the fil- bers of progeny that break out of the cell virus Asfarviridae. Giant viruses are con- trate of this treatment, giant viruses were and keep the replication cycle going. sidered to be ones with genomes larger undetected over generations of virology Viruses are supposed to be diminutive than 300 kilobase pairs and with cap- research. (Mimivirus disrupted this eva- even compared to cells that are just a mi- sid diameters of about 200 nanometers sion tactic by being so large it was visi- crometer (1,000 nanometers) in diameter. or more. ble under a light microscope.) Standard They are supposed to travel light, mak- Mimivirus is a giant among giant vi- plaquing procedures failed to report the ing do with just a few well-adapted genes. ruses, with a diameter of 750 nanome- presence of giant viruses because the In 1992, a new microorganism was iso- ters. It possesses a genome, truly outsized large particles bogged down in the soft lated from a power-plant cooling tower by viral standards, of 1.2 million base agar of the plaquing medium, disrupt- in Bradford, England, where Timothy Ro- pairs, coding an outlandish 1,018 genes. ing diffusion and the formation of visi- botham, a microbiologist at Leeds Pub- For comparison, the smallest free-liv- ble plaques. An additional explanation lic Health Laboratory, was seeking the ing bacterium, Mycoplasma genitalium, for the elusiveness of the largest viruses causative agent of a local pneumonia out- is just 450 nanometers in diameter and is that many infect protists, which have break. His search led to the warm waters possesses a genome half the size of that received far less research attention than of the cooling tower, a known reservoir in mimivirus, while coding just 482 pro- plants and animals. for bacterial pathogens in the Legionella teins. The record tiniest cellular organ- genus, which are the cause of the pneu- ism, Hodgkinia cicadicola, a parasite in monialike Legionnaire’s disease. Parti- cicadas that was described in 2009, has cles present in the sample were mistak- a genome of just 140,000 base pairs, cod- Figure 1. Giant viruses, which some call enly identified as bacteria. Gram positive ing a paltry 169 proteins. H. cicadicola is giruses in acknowledgment of their many and visible under the microscope as unable to live on its own, being entirely unique features, comprise an ancient line pathogens within the particle-gobbling dependent on the lush environment of that has been hidden in plain sight. Iron- amoeba Acanthamoeba polyphaga, the specialized cicada cells. Viruses are gen- ically, their gigantic size kept the giant vi- entities surprisingly did not generate any erally not considered living organisms ruses from being isolated by the usual fil- product from the gene-amplifying poly- (although for a consideration of their tration techniques. Shown at right is the merase chain reaction technique using position in the phylogenetic tree of life, biggest of them all (so far), mimivirus. The giant viruses possess exotic genes, universal bacterial primers. see the sidebar box in the section headed lifestyles and physiological features, Eleven years later, in 2003, the mys- “Origins”), yet mimivirus brings a bigger such as the stargate portal of mimivirus, tery organism received a new identity blueprint and more lumber to the repli- shown here wide open after the release and a new name, Acanthamoeba polyph- cation process than the living H. cicadic- of the virus’s genetic cargo. Research- aga Mimivirus, for microbe-mimick- ola and many other bacteria. ers probing the huge genomes of the gi- ing virus. Mimivirus is the largest virus Most giant viruses have only been dis- ant viruses with bioinformatics tools are ever discovered. Giant viruses had been covered and characterized in the past few learning that the picture of early life may known for a few years, many of them in a years. There are several reasons why these need adjustment to take account of these group termed nucleo-cytoplasmic large striking biological entities remained un- fascinating biological entities. DNA viruses (NCLDVs). This group fea- detected for so long. Among the most Image courtesy of Abraham Minsky, tures several other virus families, includ- consequential is that the classic tool Weizmann Institute of Science. 304 Giant Viruses 305 306 James Van Etten in American Scientist 99 (2011) collagen, the fibrous constituent of ani- mal connective tissue. Mimivirus is the only NCLDV member known to have this peripheral fiber layer. Another sin- gular feature of the mimivirus virion is a prominent five-fold star-shaped struc- ture on one icosahedral vertex called the stargate portal. Research suggests that mimivirus in- gested by an amoeba enters the cell in a membranous compartment that fuses with lysosomes, which are digestive or- ganelles. The activity of lysosomal en- zymes is predicted to cause the stargate portal to open. An internal membrane within the mimivirus then appar- ently fuses with the surrounding mem- brane compartment, forming a conduit through which the viral genome passes into the cytoplasm of the host. A viral- assembly complex called a replication Figure 2. The genomes of giant viruses can be larger than those of some bacteria. These factory then forms in the cytoplasm genomes are also packed with novelty. In the case of mimivirus (top), 86 percent of around the viral core. The replication its predicted protein-coding sequences have no known homologs with other genes in factory expands until it occupies a large gene databases. Illustration by Barbara Aulicino. Includes data provided by Alan Cann. fraction of the cell volume six hours af- ter the initial infection. With the spotlight finally on them, evolution suggests a common ancestor In the replication factory, empty, par- the giant viruses are delivering striking that likely contained a minimum set of 47 tially assembled viral capsids without lessons in viral physiology and ecology, genes that have left traces in modern vi- fibers undergo DNA packaging. Curi- not to mention challenging long-held as- ral genomes. The NCLDVs then evolved ously, DNA packaging is reported to oc- sumptions about the shape of the phylo- by losing some genes, duplicating oth- cur through faces of the viral capsid that genetic tree of life. ers and acquiring genes from their hosts are not the stargate—DNA entry into and and other organisms. The giant viruses, exit from the virion apparently occur at Big Family like other viruses, are genetic pickpock- different portals, which is very unusual Central to the placement of giant ets, grabbing genes from their hosts over for a virus. viruses in the tree of life is the pres- eons. Interpretation of viral phylogenetic In 2008, a new strain of mimivi- ence of numerous previously un- reconstructions is therefore rife with puz- rus was isolated from another cooling known virus-encoded gene families. zles. Yet a faded outline of evolutionary tower, this one in Paris. With a slightly A recent reconstruction of NCLDV history is visible. Analysis of 45 giant vi- larger genome than mimivirus, the new ruses identified five genes common to all strain was named mamavirus, and it of the NCLDV viruses and 177 additional brought with it a surprise—a parasite genes that are shared by at least two of virus named Sputnik. Viral satellites, the virus families. The ancient genetic which are quite common, are subvi- signal, however, is very weak. Consider ral agents consisting of small amounts that in a selection of three viruses in the of nucleic acid whose replication de- Phycodnaviridae family, 14 genes in com- pends on a viral genome. In this case, mon indicate a shared evolutionary his- the viral companion may be imper- tory, yet within the sprawling genomes of fectly named, since Sputnik appears these three biological entities, more than to be not merely a satellite but a legit- 1,000 total genes exist. imate parasite of its host. When pres- Mimivirus is an appropriate represen- ent, it interferes with the infectivity of tative of the giant viruses, exhibiting a va- mamavirus in amoebae and appears to riety of unique properties that point to cause the formation of defective mama- the diversity of the known giant viruses virus virions, which is not the case for and those soon to be discovered.