Principles of Virology, Volume 1. Jane Flint

virion, the prototype member of the Mimiviridae, was the first giant virus of amoebae to be discovered. Isolated from water in a cooling tower in England in 1992, it is large enough to be visible in a light microscope and was initially thought to be an intracellular bacterium within its host. Not until publication of a brief note in 2003 did it become apparent that this giant was really a virus. The mimivirus genome of 1.2 Mbp was much larger than that of any known virus at the time, exceeding that of some bacteria. This giant encodes more than 900 proteins, many of which are components of the protein translational apparatus, a function for which other viruses rely entirely on the host.

      Since reports of the first giant viruses, the use of different strains of amoebae to screen soil and water samples from diverse environments and geographic locations has yielded more than 50 isolates, assigned to nine distinct families. Among the most spectacular is a Pandoravirus isolate, discovered in saltwater off the coast of Chile in 2013. The genome of this giant is twice the size of the mimivirus genome, and contains ∼2,500 putative protein-coding sequences, most of them never seen before. Furthermore, while mimivirus has a more or less familiar icosahedral capsid, the Pandoravirus has no regular capsid. Instead, the genomes of these viruses are surrounded by an ovoid envelope, with a pore at the apex that allows delivery of the internal components into the cytoplasm of its host. The following year two additional giant amoeba viruses, a circular mollivirus and ovoid pithovirus, were discovered in a sample of Siberian permafrost more than 30,000 years old.

      The unusual properties of the giant viruses of amoebae have prompted the somewhat controversial speculation that they might represent a separate branch in the tree of life, or that they arose by reductive evolution from the nucleus of a primitive cellular life form. However, the discovery in 2017 of another group of these viruses, by metagenomic analysis of samples from a sewer in Klosterneuburg, Austria, has suggested a more pedestrian origin. While the new group, called Klosneuviruses, encode numerous components of translational machinery, comprehensive phylogenetic analyses indicate that these genes were captured from a cellular host by a smaller, precursor virus during evolution of Klosneuviruses. If this is a general phenomenon, the 2018 description of tailed mimivirus relatives, isolated from the extreme environments of an alkaline soda lake in Brazil and from deep in the Atlantic Ocean, must be considered an extraordinary example of such capture. The genomes of these odd-looking isolates, called Tupanviruses, contain nearly all of the necessary translation-associated genes, lacking only ribosomes for protein synthesis. It would seem that there is still much to ponder concerning the evolution of these giant viruses.

      Properties of some of the largest currently known giants, all of which infect amoebae, with representative vertebrate-infecting DNA viruses, of which poxviruses are the largest. The broad range of nucleic acid composition among the amoeba viral genomes is illustrated by the substantial differences in their G+C content. The number of known or putative coding genes in each viral genome is listed. Examples of small, medium, and large mammalian viruses (poliovirus, herpesvirus, and vaccinia virus, respectively) are included for comparison.

      For illustrations of giant amoeba virus structures, see http://viralzone.expasy.org/all_by_species/670.html. See also TWiV 261: Giants among viruses. Interview with Drs. Chantal Abergel and Jean-Michel Claverie at http://www.microbe.tv/twiv/twiv-261-giants -among-viruses/.

       Abrahão J, Silva L, Silva LS, Khalil JYB, Rodrigues R, Arantes T, Assis F, Boratto P, Andrade M, Kroon EG, Ribeiro B, Bergier I, Seligmann H, Ghigo E, Colson P, Levasseur A, Kroemer G, Raoult D, La Scola B. 2018. Tailed giant Tupanvirus possesses the most complete translational apparatus of the known virosphere. Nat Commun 9:749–761.

       Colson P, La Scola B, Levasseur A, Caetano-Anollés G, Raoult D. 2017. Mimivirus: leading the way in the discovery of giant viruses of amoebae. Nat Rev Microbiol 15:243–254.

       Colson P, La Scola B, Raoult D. 2017. Giant viruses of amoebae: a journey through innovative research and paradigm changes. Annu Rev Virol 4:61–85.

       Racaniello V. 8 March 2018. Only the ribosome is lacking. Virology Blog. http://www.virology.ws/2018/03/08/only-the-ribosome-is-lacking/.

       Schulz F, Yutin N, Ivanova NN, Ortega DR, Lee TK, Vierheilig J, Daims H, Horn M, Wagner M, Jensen GJ, Kyrpides NC, Koonin EV, Woyke T. 2017. Giant viruses with an expanded complement of translation system components. Science 356:82–85.

Figure 1.12 The Baltimore classification. The Baltimore classification assigns viruses to seven (I to VII) distinct classes on the basis of the nature and polarity of their genomes. Because all viruses must produce mRNA that can be translated by cellular ribosomes, knowledge of the composition of a viral genome provides insight into the pathways required to produce mRNA, indicated by arrows. See also Baltimore D. 1971. Bacteriol Rev 35:235–241.

      By convention, mRNA is defined as a positive [(+)] strand because it contains immediately translatable information. In the Baltimore classification, a strand of DNA that is of equivalent sequence is also designated a (+) strand. The RNA and DNA complements of (+) strands are designated negative [(−)] strands.

      As originally conceived, the Baltimore scheme included six classes of viral genomes (designated I to VI). When the gapped DNA genome of hepadnaviruses (e.g., hepatitis B virus) was discovered, these viruses were assigned to a seventh class (VII). The DNA and RNA descriptors for the viral classes [single-stranded DNA (ssDNA), double-stranded DNA (dsDNA), (+) RNA, or (–) RNA, etc.], but not the Roman numeral designations, have been adopted universally and are a valuable complement to classical taxonomy. The information embodied in classification by genome type provides virologists with immediate insight into the steps that must take place to initiate the replication and expression of any viral genome.

Because the viral genome carries the entire blueprint for virus propagation, molecular virologists have long considered it the most important characteristic for classification purposes. Although individual virus families are known by their classical designations, they are commonly grouped according to their genome type. In the ICTV compilation, all viral families are assigned to one of the seven classes described in the Baltimore system (Fig. 1.13).

A Common Strategy for Viral Propagation

      The basic thesis of this textbook is that all viral propagation can be described in the context of three fundamental properties.

       Viral genomes are packaged inside particles that mediate their transmission from host to host.

       The viral genome contains the information for initiating and completing an infectious cycle within a susceptible, permissive cell.

       An infectious cycle includes attachment and entry, decoding of genome information, genome replication, and assembly and release of particles containing the genome.

       Viral propagation is ensured by establishment in a host population.

Perspectives

The study of viruses has increased our understanding of the importance and ubiquitous existence of these diverse agents and, in many cases, yielded new and unexpected insight into the molecular biology of host cells and organisms. Indeed, because viruses are obligate molecular parasites, every tactical solution encountered in their reproduction and propagation must of necessity tell us something about