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