The Baltimore Classification of Viruses 50 Years Later: How Does It Stand in the Light of Virus Evolution?

Abstract

Fifty years ago, David Baltimore published a brief conceptual paper delineating the classification of viruses by the routes of genome expression. The six "Baltimore classes" of viruses, with a subsequently added 7th class, became the conceptual framework for the development of virology during the next five decades. During this time, it became clear that the Baltimore classes, with relatively minor additions, indeed cover the diversity of virus genome expression schemes that also define the replication cycles. Here, we examine the status of the Baltimore classes 50 years after their advent and explore their links with the global ecology and biology of the respective viruses. We discuss an extension of the Baltimore scheme and why many logically admissible expression-replication schemes do not appear to be realized in nature. Recent phylogenomic analyses allow tracing the complex connections between the Baltimore classes and the monophyletic realms of viruses. The five classes of RNA viruses and reverse-transcribing viruses share an origin, whereas both the single-stranded DNA viruses and double-stranded DNA (dsDNA) viruses evolved on multiple independent occasions. Most of the Baltimore classes of viruses probably emerged during the earliest era of life evolution, at the stage of the primordial pool of diverse replicators, and before the advent of modern-like cells with large dsDNA genomes. The Baltimore classes remain an integral part of the conceptual foundation of biology, providing the essential structure for the logical space of information transfer processes, which is nontrivially connected with the routes of evolution of viruses and other replicators.

Keywords: virus classification; virus evolution; virus realms; virus taxonomy.

FIG 1

The central dogma of molecular biology. The figure is redrawn from Crick’s 1970 article. The solid arrows represent the mainstream routes of information flow, and the dashed arrows show (putative) “special routes” after Crick. Adapted from reference with permission of Springer Nature.

FIG 2

The amended scheme of the seven Baltimore classes of viruses. Shown is the transfer of genetic information between genomic nucleic acids encapsidated into virions (genomes, for short) and mRNA. This transfer is enabled by enzymatic reactions; in the case of the RNA viruses, with the exception of hepatitis delta and related viruses, these reactions are catalyzed by the virus-encoded RNA-dependent RNA polymerases, which are encapsidated into virions of viruses of BCIII and BCV, but not BCIV; reverse-transcription of RNA to DNA is catalyzed by virus-encoded reverse transcriptases, which may or may not be encapsidated into virions; replication of DNA genomes is catalyzed by virus-encoded or host-encoded DNA polymerases, which are not encapsidated. The roman numerals denote the BCs. BCVII was added to the scheme. Adapted from reference with permission.

FIG 3

The host range distribution in the seven Baltimore classes of viruses. (A) Distribution of the BCs in the three cellular domains. The panel illustrates the dominance of dsDNA viruses in Bacteria and Archaea, which contrasts the dominance of viruses with RNA genomes in Eukarya. (B) Distribution of the BCs in eukaryotes. Each circle represents the breakdown of the virus genera (according to the ICTV taxonomy release number 35 [https://talk.ictvonline.org/files/master-species-lists/m/msl/9601]) associated with the indicated group of hosts. The number of virus genera (n) is indicated inside each circle. The BCs are denoted by the virion nucleic acid and are color coded.

FIG 4

The extended, hierarchical version of virus classification by information transmission routes. Types DDR, DRRD, RR, DRD, DDRD, and RRD represent theoretical paths of genetic information transfer. The elementary acts of synthesis of DNA or RNA on a DNA template are denoted, respectively, as DD or DR, and the elementary acts of synthesis of DNA or RNA on an RNA template are denoted as RD and RR. Each type is further divided into superclasses, denoted with Latin letters, and the superclasses are divided into classes denoted with Arabic numerals and shown in separate boxes. In each class, the leftmost genetic unit, shown in red, represents the virion nucleic acid (genome). The occupied classes are shown by colored background, green for those known at the time of the original publication (58) and yellow for those discovered subsequently (see the text for details). The blue arrows show synthesis of single-stranded molecules on double-stranded templates (multiplicational acts of synthesis), and black arrows show synthesis of dsDNA or dsRNA on single-stranded templates (nonmultiplicational acts of synthesis). Abbreviations: D, DNA; R, RNA. For each occupied class, the corresponding BC is indicated in the bottom left corner, whereas examples of virus families that use the corresponding routes of information transfer are shown in parentheses. The examples were chosen arbitrarily. Class DDR-d2 is currently not occupied by known viruses, but the corresponding flow of information has been described for conjugative F-like plasmids. Reproduced from reference with permission from Elsevier.

FIG 5

The Baltimore classes and monophyletic realms of viruses. The connections between the BCs and the virus realms are shown by colored edges. Thick lines denote major associations, and thin lines denote exceptional cases (see the text for details). For each virus realm, a ribbon diagram of a hallmark structure is shown as follows: Riboviria, poliovirus RdRP (1RA7); Ribozyviria, HDV ribozyme (4PRF); Monodnaviria, porcine circovirus 2 rolling circle replication initiation endonuclease (5XOR); Adnaviria, major capsid protein of Sulfolobus rod-shaped virus 2 (3J9X); Duplodnaviria, major capsid protein of bacteriophage HK97 (1OHG); Varidnaviria, double jelly roll major capsid protein of bacteriophage PRD1 (1HX6). The protein structures are colored by secondary structure: α-helices, green; β-strands, red.

FIG 6

The Baltimore classes and evolution of the primordial replicator pool. Shading shows the primordial replicator pool; the dark hue for (+)RNA shows that this genome structure was, most likely, the first on the route from the primordial RNA world to diverse genetic systems. Solid arrows show the inferred origins of different types of replicators, and empty block arrows show origin of viruses belonging to each of the BCs and cellular organisms. Abbreviations: DdDP, DNA-dependent DNA polymerase; DdRP, DNA-directed RNA polymerase; RdRP, RNA-dependent RNA polymerase; RCRE, rolling circle replication initiation endonuclease; RT, reverse transcriptase.