Virus classification system made by David Baltimore
Baltimore classification is a system used to classify viruses based on their manner of messenger RNA (mRNA) synthesis. By organizing viruses based on their manner of mRNA production, it is possible to study viruses that behave similarly as a distinct group. Seven Baltimore groups are described that take into consideration whether the viral genome is made of deoxyribonucleic acid (DNA) or ribonucleic acid (RNA), whether the genome is single- or double-stranded, and whether the sense of a single-stranded RNA genome is positive or negative.
Baltimore classification also closely corresponds to the manner of replicating the genome, so Baltimore classification is useful for grouping viruses together for both transcription and replication. Certain subjects pertaining to viruses are associated with multiple, specific Baltimore groups, such as specific forms of translation of mRNA and the host range of different types of viruses. Structural characteristics such as the shape of the viral capsid, which stores the viral genome, and the evolutionary history of viruses are not necessarily related to Baltimore groups.
Baltimore classification was created in 1971 by virologist David Baltimore. Since then, it has become common among virologists to use Baltimore classification alongside standard virus taxonomy, which is based on evolutionary history. In 2018 and 2019, Baltimore classification was partially integrated into virus taxonomy based on evidence that certain groups were descended from common ancestors. Various realms, kingdoms, and phyla now correspond to specific Baltimore groups.
Overview.
Baltimore classification groups viruses together based on their manner of mRNA synthesis. Characteristics directly related to this include whether the genome is made of deoxyribonucleic acid (DNA) or ribonucleic acid (RNA), the strandedness of the genome, which can be either single- or double-stranded, and the sense of a single-stranded genome, which is either positive or negative. The primary advantage of Baltimore classification is that by classifying viruses according to the aforementioned characteristics, viruses that behave in the same manner can be studied as distinct groups. There are seven Baltimore groups numbered with Roman numerals, listed hereafter.
Baltimore classification is chiefly based on the transcription of the viral genome, and viruses within each group typically share the manners 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. Because of this, Baltimore classification provides insights into both the transcription and replication parts of the viral life cycle. Structural characteristics of a virus particle, called a virion, such as the shape of the viral capsid 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.
Classification.
DNA viruses.
DNA viruses have genomes made of deoxyribonucleic acid (DNA) and are organized into two groups: double-stranded DNA (dsDNA) viruses, and single-stranded DNA (ssDNA) viruses. They are assigned to four separate realms: "Adnaviria", "Duplodnaviria", "Monodnaviria", and "Varidnaviria". Many have yet to be assigned to a realm.
Group I: double-stranded DNA viruses.
The first Baltimore group contains viruses that have a double-stranded DNA (dsDNA) 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 site where transcription begins, allowing for the recruitment of a host RNA polymerase. Second, once the RNA polymerase is recruited, it uses the negative strand as a template for synthesizing mRNA strands. Third, the RNA polymerase terminates transcription upon reaching a specific signal, such as a polyadenylation site.
dsDNA viruses make use of several mechanisms to replicate their genome. Bidirectional replication, in which two replication forks are established at a replication origin site and move in opposite directions of each other, is widely used. A rolling circle mechanism that produces linear strands while progressing in a loop around the circular genome is also common. Some 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 prior synthesized strand, forming a dsDNA genome. Lastly, some dsDNA viruses are replicated as part of a process called replicative transposition whereby a viral genome in a host cell's DNA is replicated to another part of a host genome.
dsDNA viruses can be subdivided between 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 the cytoplasm, in which case they have evolved or acquired their own means of executing transcription and replication. dsDNA viruses are also commonly divided between tailed dsDNA viruses, referring to members of the realm "Duplodnaviria", usually the tailed bacteriophages of the order "Caudovirales", and tailless or non-tailed dsDNA viruses of the realm "Varidnaviria".
dsDNA viruses are classified into three of the four realms and include many taxa that are unassigned to a realm:
Group II: single-stranded DNA viruses.
The second Baltimore group contains viruses that have a single-stranded DNA (ssDNA) 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 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 replication of the viral genome. Eukaryotic ssDNA viruses are replicated in the nucleus.
Most ssDNA viruses contain circular genomes that are replicated via rolling circle replication (RCR). ssDNA RCR is initiated by an endonuclease that bonds to and cleaves the positive strand, allowing a DNA polymerase to use the negative strand as a template for replication. Replication progresses in a loop around the genome by means of extending the 3′-end of the positive strand, displacing the prior positive strand, and the endonuclease cleaves the positive strand again to create a standalone genome that is ligated into a circular loop. The new ssDNA may be packaged into virions or replicated by a DNA polymerase to form a double-stranded form for transcription or continuation of the replication cycle.
Parvoviruses contain linear ssDNA genomes that are replicated via rolling hairpin replication (RHR), which is similar to RCR. Parvovirus 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 genome, producing numerous copies of the genome in a continuous process. Individual genomes are then excised from this molecule by the viral endonuclease. For parvoviruses, either the positive or negative sense strand may be packaged into capsids, varying from virus to virus.
Nearly all ssDNA viruses have positive sense genomes, but a few exceptions and peculiarities exist. The family "Anelloviridae" is the only ssDNA family whose members have negative sense genomes, which are circular. Parvoviruses, as previously mentioned, may package either the positive or negative sense strand into virions. Lastly, bidnaviruses package both the positive and negative linear strands. In any case, the sense of ssDNA viruses, unlike for ssRNA viruses, is not sufficient to separate ssDNA viruses into two groups since all ssDNA viral genomes are converted to dsDNA forms prior to transcription and replication.
ssDNA viruses are classified into one of the four realms and include several families that are unassigned to a realm:
RNA viruses.
RNA viruses have genomes made of ribonucleic acid (RNA) and comprise three groups: double-stranded RNA (dsRNA) viruses, positive sense single-stranded RNA (+ssRNA) viruses, and negative sense single-stranded RNA (-ssRNA) viruses. The majority of RNA viruses are classified in the kingdom "Orthornavirae" in the realm "Riboviria". The exceptions are generally viroids and other subviral agents. Some of the latter category, such as the hepatitis D virus, are classified in the realm "Ribozyviria".
Group III: double-stranded RNA viruses.
The third Baltimore group contains viruses that have a double-stranded RNA (dsRNA) genome. After entering a host cell, the dsRNA genome is transcribed to mRNA from the negative strand by the viral RNA-dependent RNA polymerase (RdRp). The mRNA may be used for translation or replication. Single-stranded mRNA is replicated to form the dsRNA genome. The 5′-end of the genome may be naked, capped, or covalently bound to a viral protein.
dsRNA is not a molecule made by cells, so cellular life has evolved antiviral systems to detect and inactivate viral dsRNA. To counteract this, many dsRNA genomes are constructed inside of capsids, thereby avoiding detection inside of the host cell's cytoplasm. mRNA is forced out from the capsid in order to be translated or to be translocated from a mature capsid to a progeny capsid. While dsRNA viruses typically have capsids, viruses in the families "Amalgaviridae" and "Endornaviridae" have not been observed to form virions and as such apparently lack capsids. Endornaviruses are also unusual in that unlike other RNA viruses, they possess a single, long open reading frame (ORF), or translatable portion, and a site-specific nick in the 5′ region of the positive strand.
dsRNA viruses are classified into two phyla within the kingdom "Orthornavirae" of the realm "Riboviria":
Group IV: positive sense single-stranded RNA viruses.
The fourth Baltimore group contains viruses that have a positive sense single-stranded RNA (+ssRNA) genome. For +ssRNA viruses, the genome functions as mRNA, so no transcription is required for translation. +ssRNA viruses will also, however, produce positive sense copies of the genome from negative sense strands of an intermediate dsRNA genome. This acts as both a transcription and a replication process since the replicated RNA is also mRNA. The 5′-end may be naked, capped, or covalently bound to a viral protein, and the 3′-end may be naked or polyadenylated.
Many +ssRNA viruses are able to have only a portion of their genome transcribed. Typically, subgenomic RNA (sgRNA) strands are used for translation of structural and movement proteins needed during intermediate and late stages of infection. sgRNA transcription may occur by commencing RNA synthesis within the genome rather than from the 5′-end, by stopping RNA synthesis at specific sequences in the genome, or by, as a part of both prior methods, synthesizing leader sequences from the viral RNA that are then attached to sgRNA strands. Because replication is required for sgRNA synthesis, RdRp is always translated first.
Because the process of replicating the viral genome produces intermediate dsRNA molecules, +ssRNA viruses can be targeted by the host cell's immune system. To avoid detection, +ssRNA viruses replicate in membrane-associated vesicles that are used as replication factories. From there, only viral +ssRNA, which may be mRNA, enters the main cytoplasmic area of the cell.
+ssRNA viruses can be subdivided between those that have polycistronic mRNA, which encodes a polyprotein that is cleaved to form multiple mature proteins, and those that produce subgenomic mRNAs and therefore undergo two or more rounds of translation. +ssRNA viruses are included in three phyla in the kingdom "Orthornavirae" in the realm "Riboviria":
Group V: negative sense single-stranded RNA viruses.
The fifth Baltimore group contains viruses that have a negative sense, single-stranded RNA (-ssRNA) genome. mRNA, which is positive sense, is transcribed directly from the negative sense genome. The first process for -ssRNA transcription involves RdRp binding to a leader sequence on the 3′ end of the genome, transcribing a 5′ triphosphate-leader RNA that is capped, then stopping and restarting on a transcription signal which is capped, continuing until a stop signal is reached. The second manner is similar but instead of synthesizing a cap, RdRp may make use of cap snatching, whereby a short sequence of host cell mRNA is taken and used as the 5′ cap of the viral mRNA. Genomic -ssRNA is replicated from the positive sense antigenome in a similar manner as transcription, except in reverse using the antigenome as a template for the genome. RdRp moves from the 3′-end to the 5′-end of the antigenome and ignores all transcription signals when synthesizing genomic -ssRNA.
Various -ssRNA viruses use special mechanisms for transcription. The manner of producing the polyA tail may be via polymerase stuttering, during which RdRp transcribes an adenine from uracil and then moves back in the RNA sequence with the mRNA to transcribe it again, continuing this process numerous times until hundreds of adenines have been added to the 3′-end of the mRNA. Additionally, some -ssRNA viruses are ambisense, as both the positive and negative strands separately encode viral proteins, and these viruses produce two separate mRNA strands: one directly