Baltimore classification


Baltimore classification is a system used to classify viruses by their routes of transferring genetic information from the genome to messenger RNA. Seven Baltimore groups, or classes, exist and are numbered in Roman numerals from I to VII. Groups are defined by whether the viral genome is made of deoxyribonucleic acid or ribonucleic acid, whether the genome is single- or double-stranded, whether a single-stranded RNA genome is positive-sense or negative-sense, and whether the virus makes DNA from RNA. Viruses within Baltimore groups typically have the same replication method, but other characteristics such as virion structure are not directly related to Baltimore classification.
The seven Baltimore groups are for double-stranded DNA viruses, single-stranded DNA viruses, double-stranded RNA viruses, positive-sense single-stranded RNA viruses, negative-sense single-stranded RNA viruses, ssRNA viruses that have a DNA intermediate in their life cycle, and dsDNA viruses that have an RNA intermediate in their life cycle. Only one class exists for ssDNA viruses because their genomes are converted to dsDNA before transcription regardless of sense. Some viruses belong to more than one Baltimore group, such as DNA viruses that have either dsDNA or ssDNA as their genome.
Many virus characteristics do not define which Baltimore group they belong to but do correlate to specific Baltimore groups. This includes the use of RNA editing and alternative splicing, whether the virus's genome is segmented, the size and structure of the virus's genome, the host range of viruses, whether the virus packages replication and transcription machinery into virions, and unorthodox methods of translating mRNA into proteins. Furthermore, while Baltimore groups were not established based on evolutionary relationships, research in the 21st century has found that certain groups, such as dsRNA, +ssRNA, and many –ssRNA viruses, share common ancestry.
Baltimore classification was created in 1971 by virologist David Baltimore and initially only included the first six groups. It was later expanded to include group VII after the discovery of dsDNA-RT viruses. Since then, it has become common among virologists to use Baltimore classification alongside virus taxonomy due to its utility. In 2018 and 2019, Baltimore classification was partially integrated into virus taxonomy based on evidence that certain groups were descended from common ancestors. Various taxa now correspond to specific Baltimore groups. An extension of Baltimore classification has been proposed by virologist Vadim Agol to encompass all possible routes of genetic information transmission.

Overview

Baltimore classification groups viruses together by their routes of transferring genetic information from the genome to messenger RNA. Characteristics that determine the Baltimore group of a virus include whether the genome is made of deoxyribonucleic acid or ribonucleic acid, the strandedness of the genome, which can be either single- or double-stranded, the sense of a single-stranded RNA genome, which can be either positive or negative, and whether the virus synthesizes DNA from RNA. There are seven Baltimore groups or classes, numbered with Roman numerals, listed hereafter.
  • Group I: double-stranded DNA viruses
  • Group II: single-stranded DNA viruses
  • Group III: double-stranded RNA viruses
  • Group IV: positive-sense single-stranded RNA viruses
  • Group V: negative-sense single-stranded RNA viruses
  • Group VI: single-stranded RNA viruses with a DNA intermediate in their life cycle
  • Group VII: double-stranded DNA viruses with an RNA intermediate in their life cycle
Baltimore classification is chiefly based on the path toward transcription of the viral genome, and viruses within each group usually share the manner by which the mRNA synthesis occurs. While not the direct focus of Baltimore classification, groups are organized in such a manner that viruses in each group also typically have the same mechanisms of replicating the viral genome. Structural characteristics of the extracellular virus particle, called a virion, such as the shape of the viral capsid, which stores the genome, and the presence of a viral envelope, a lipid membrane that surrounds the capsid, have no direct relation to Baltimore groups, nor do the groups necessarily show genetic relation based on evolutionary history.

Baltimore groups

Group I: double-stranded DNA viruses

The first Baltimore group contains viruses that have a double-stranded DNA genome. All dsDNA viruses have their mRNA synthesized in a three-step process. First, a transcription preinitiation complex binds to the DNA upstream of the transcription site, recruiting a host RNA polymerase enzyme. Once the RNA polymerase is recruited, it uses the negative-sense strand as a template for synthesizing mRNA strands, which are positive sense. The RNA polymerase then terminates transcription upon reaching a specific signal, such as a polyadenylation site.
dsDNA viruses make use of several mechanisms to replicate their genome. A widely used method is bidirectional replication, in which two replication forks are established at a replication origin site and move in opposite directions on a DNA molecule. A rolling circle mechanism that produces linear strands while progressing in a loop around a circular genome is also common. Many dsDNA viruses use a strand displacement method whereby one strand is synthesized from a template strand, and a complementary strand is then synthesized from the previously synthesized strand to form a dsDNA genome. Lastly, some dsDNA viruses are replicated as part of a process called replicative transposition, whereby a viral genome that is integrated into a host cell's genome is replicated to another part of the host cell's genome.
dsDNA viruses can be divided informally into those that replicate in the nucleus, and as such are relatively dependent on host cell machinery for transcription and replication, and those that replicate in cytoplasm, in which case they have obtained their own means of transcription and replication. dsDNA viruses are also sometimes divided between tailed dsDNA viruses, which refers to members of the realm Duplodnaviria, specifically the head-tail of the class Caudoviricetes, and tailless or non-tailed dsDNA viruses, which refers to viruses in the realms Singelaviria and Varidnaviria.
dsDNA viruses are classified into five realms and include many taxa that are unassigned to a realm:
  • Viruses in the realms Adnaviria, Duplodnaviria, and Singelaviria are dsDNA viruses.
  • In the realm Monodnaviria, members of the class Papovaviricetes are dsDNA viruses.
  • Viruses in the realm Varidnaviria are dsDNA viruses except for the class Ainoaviricetes, which are ssDNA viruses.
  • The following taxa that are unassigned to a realm exclusively contain dsDNA viruses:
  • * Classes: Naldaviricetes
  • * Families: Ampullaviridae, Bicaudaviridae, Clavaviridae, Eurekaviridae, Fuselloviridae, Globuloviridae, Guttaviridae, Halspiviridae, Huangdiviridae, Itzamnaviridae, Ovaliviridae, Plasmaviridae, Portogloboviridae, Thaspiviridae
  • * Genera: Dinodnavirus, Rhizidiovirus
  • Lastly, the unassigned family Nipumfusiviridae contains both dsDNA and ssDNA viruses.

    Group II: single-stranded DNA viruses

The second Baltimore group contains viruses that have a single-stranded DNA genome. ssDNA viruses have the same manner of transcription as dsDNA viruses. Because the genome is single-stranded, however, it is first made into a double-stranded form by a DNA polymerase enzyme upon entering a host cell. mRNA is then synthesized from the double-stranded form. The double-stranded form of ssDNA viruses may be produced either directly after entry into a cell or as a consequence of replicating the viral genome.
Most ssDNA viruses contain circular genomes that are replicated by rolling circle replication. ssDNA RCR is initiated by an endonuclease enzyme that bonds to and cleaves the positive-sense strand, which allows a DNA polymerase to use the negative-sense strand as a template for replication. Replication progresses in a loop around the genome by extending the 3′-end of the positive-sense strand, which displaces the prior positive-sense strand. The endonuclease then cleaves the positive-sense strand again to create a standalone genome that is joined into a circular loop. The new ssDNA genome may be packaged into virions or replicated by a DNA polymerase to create a double-stranded form for transcription or additional rounds of replication.
Parvoviruses and bidnaviruses have linear ssDNA genomes that are replicated by rolling hairpin replication, which is similar to RCR. Their genomes have hairpin loops at each end of the genome that repeatedly unfold and refold during replication to change the direction of DNA synthesis to move back and forth along the linear genome, which produces numerous copies of the genome in a continuous process. Individual genomes are then excised from this molecule by the endonuclease.
Nearly all ssDNA viruses have positive-sense genomes, but a few exceptions and peculiarities exist. Anelloviruses are the only ssDNA viruses that have negative-sense genomes. Parvoviruses may package either the positive- or negative-sense strand into capsids. Lastly, bidnaviruses may package both the positive- and negative-sense strands of their bipartite genome. In any case, the sense of ssDNA viruses, unlike that of ssRNA viruses, is not sufficient to separate ssDNA viruses into two Baltimore groups since all ssDNA viral genomes are converted to dsDNA forms before transcription and replication.
ssDNA viruses are classified into two realms and include a few families that are unassigned to realms:
  • In the realm Monodnaviria, members are ssDNA viruses except for viruses in the class Papovaviricetes, which are dsDNA viruses.
  • In the realm Varidnaviria, viruses of the class Ainoaviricetes are ssDNA viruses.
  • The unassigned families Obscuriviridae and Spiraviridae are ssDNA virus families.
  • Lastly, the unassigned family Nipumfusiviridae contains both ssDNA and dsDNA viruses.