TWiV 357: Mistletoe on the Tree of Life

On episode #357 of the science show This Week in Virology, Jens Kuhn joins the TWiVomics to discuss the strengths and weaknesses of viral taxonomy, including its history and evolution, how viruses are ordered, and why T. rex was classified without having a living isolate.

You can find TWiV #357 at

Simplifying virus classification: The Baltimore system

baltimore-classificationAlthough many viruses are classified into individual families based on a variety of physical and biological criteria, they may also be placed in groups according to the type of genome in the virion. Over 30 years ago virologist David Baltimore devised an alternative classification scheme that takes into account the nature of the viral nucleic acid.

One of the most significant advances in virology of the past 30 years has been the understanding of how viral genomes are expressed. Cellular genes are encoded in dsDNA, from which mRNAs are produced to direct the synthesis of protein. Francis Crick conceptualized this flow of information as the central dogma of molecular biology:

DNA —> RNA —> protein

All viruses must direct the synthesis of mRNA to produce proteins. No viral genome encodes a complete system for translating proteins; therefore all viral protein synthesis is completely dependent upon the translational machinery of the cell. Baltimore created his virus classification scheme based on the central role of the translational machinery and the importance of viral mRNAs in programming viral protein synthesis. In this scheme, he placed mRNA in the center, and described the pathways to mRNA from DNA or RNA genomes. This arrangement highlights the obligatory relationship between the viral genome and its mRNA.

By convention, mRNA is defined as a positive (+) strand because it is the template for protein synthesis. A strand of DNA of the equivalent sequence is also called the (+) strand. RNA and DNA strands that are complementary to the (+) strand are, of course, called negative (-) strands.

When originally conceived, the Baltimore scheme encompassed six classes of viral genome, as shown in the figure.  Subsequently the gapped DNA genome of hepadnaviruses (e.g. hepatitis B virus) was discovered. The genomes of these viruses comprise the seventh class.  During replication, the gapped DNA genome is filled in to produce perfect duplexes, because host RNA polymerase can only produce mRNA from a fully double-stranded template.

The Baltimore classification system is an elegant molecular algorithm for virologists. The principles embodied in the scheme are extremely useful for understanding information flow of viruses with different genome configurations. When the bewildering array of viruses is classified by this system, we find fewer than 10 pathways to mRNA. By knowing only the nature of the viral genome, the basic steps that must occur to produce mRNA are readily apparent. More pragmatically, the system simplifies understanding the extraordinary life cycle of viruses.

Crick FH (1958). On protein synthesis. Symposia of the Society for Experimental Biology, 12, 138-63 PMID: 13580867

Baltimore D (1971). Expression of animal virus genomes. Bacteriological reviews, 35 (3), 235-41 PMID: 4329869

How viruses are classified

virosphere-2005For the first 60 years of virus discovery, there was no system for classifying viruses. Consequently viruses were named haphazardly, a practice that continues today.

Vertebrate viruses may be named according to the associated diseases (poliovirus, rabies), the type of disease caused (murine leukemia virus), or the sites in the body affected or from which the virus was first isolated (rhinovirus, adenovirus). Some viruses are named for where they were first isolated (Sendai virus, Coxsackievirus), for the scientists who discovered them (Epstein-Barr virus), or for the way people imagined they were contracted (dengue = ‘evil spirit’; influenza = ‘influence’ of bad air).

By the early 1960s, new viruses were being discovered and studied by electron microscopy. As particles of different sizes, shapes, and composition were identified, it became clear that a systematic nomenclature was needed. Lwoff, Horne, and Tournier suggested a comprehensive scheme for classifying all viruses in 1962. Their proposal used the classical Linnaean hierarchical system of phylum, class, order, family, genus and species. The complete scheme was not adopted, but animal viruses were soon classified by family, genus, and species.

An important part of the scheme proposed by Lwoff and colleagues is that viruses are grouped according to their properties, not the cells they infect. The nucleic acid genome was also recognized as a primary criterion for classification. Four characteristics were to be used for the classification of all viruses:

  1. Nature of the nucleic acid in the virion
  2. Symmetry of the protein shell
  3. Presence or absence of a lipid membrane
  4. Dimensions of the virion and capsid

Other characteristics which were subsequently added include the type of disease caused, and which animals and tissues are infected. With the development of nucleic acid sequencing technologies in the 1970s, genomics has played an increasingly important role in taxonomy. Today new viruses are assigned to families based on the nucleic acid sequence of their genome.

The International Committee on the Taxonomy of Viruses (ICTV) is charged with the task of developing, refining, and maintaining a universal virus taxonomy. A complete catalog of known viruses is maintained by the ICTV at ICTVdb. Although the ICTV nomenclature is used to classify animals viruses, plant virologists do not place their viruses into families and genera, but use group names derived from the prototype virus.

Because the viral genome carries the blueprint for producing new viruses, virologists consider it the most important characteristic for classification. Next we’ll discuss the Baltimore classification, an alternative scheme based on the viral genome.

Lwoff, A., Horne, R., & Tournier, P. (1962). A system of viruses. Cold Spring Harb Symp Quant Biol., 27, 51-55

Buchen-Osmond, C. (2003). The universal virus database ICTVdB Computing in Science & Engineering, 5 (3), 16-25 DOI: 10.1109/MCISE.2003.1196303

Europic 2008

Since Monday I have been in Sitges, Spain for Europic 2008. This is a scientific meeting on picornaviruses held every other year in a European country. The picornaviruses are a family of non-enveloped, positive-strand RNA viruses, and includes poliovirus, rhinovirus, and foot-and-mouth disease virus.

I have been attending Europic meetings since 1983, when it was held in Urbino, Italy. Not only is the science excellent and focussed, but the venues are fabulous. Sitges is a lovely town on the coast of the Mediterranean. While the sessions leave little time for seeing the town, it is nice to be in a different place, with old buildings, culture, and a history.

We have already held sessions on virus entry into cells, epidemiology, surveillance, and evolution. I learned yesterday that virus classification is now entirely based on sequence comparisons, with little concern for the biology of the virus. For example, the rhinovirus and enterovirus genera will be combined into one genus called enterovirus. While this change reflects the sequence relationships among the viruses, it will surely be hard to explain why respiratory viruses (rhinoviruses) are classified in a genus whose name implies replication in the enteric tract (enterovirus). The proposed changes in classification can be viewed here.

Another interesting topic was serotyping. Many years ago, new viruses were classified according to an immunological definition: If antiserum against one virus did not neutralize the infectivity of a related virus, they were said to be different serotypes. Modern sequence analyses now indicate that different serotypes are often highly related. Therefore the use of an antigenic classification is somewhat outdated. Sequence analysis will now be used to define serotype, and the different viruses will now be called types, rather than serotypes.

These changes reflect the growing influence of genomics on virology.