DNA virus: Difference between revisions

{{shortShort description|Virus that has DNA as its genetic material}}

A '''DNA virus''' is a [[virus]] that has a [[genome]] made of [[deoxyribonucleic acid]] (DNA) that is replicated by a [[DNA polymerase]]. They can be divided between those that have two strands of DNA in their genome, called double-stranded DNA (dsDNA) viruses, and those that have one strand of DNA in their genome, called single-stranded DNA (ssDNA) viruses. dsDNA viruses primarily belong to two [[Realm (virology)|realms]]: ''[[Duplodnaviria]]'' and ''[[Varidnaviria]]'', and ssDNA viruses are almost exclusively assigned to the realm ''[[Monodnaviria]]'', which also includes some dsDNA viruses. Additionally, many DNA viruses are unassigned to higher taxa. VirusesReverse thattranscribing viruses, which have a DNA genome that is replicated through an RNA intermediate by a [[reverse transcriptase]], are separatelyclassified considered reverse transcribing viruses and are assigned tointo the kingdom ''[[Pararnavirae]]'' in the realm ''[[Riboviria]]''.

DNA viruses are ubiquitous worldwide, especially in marine environments where they form an important part of marine ecosystems, and infect both [[prokaryote]]s and [[eukaryote]]s. They appear to have multiple origins, as viruses in ''Monodnaviria'' appear to have emerged from archaeal and bacterial [[plasmid]]s on multiple occasions, though the origins of ''Duplodnaviria'' and ''Varidnaviria'' are less clear. Prominent disease-causing DNA viruses include [[Herpesvirales|herpesviruses]], [[Papillomaviridae|papillomaviruses]], and [[Poxviridae|poxviruses]].

The [[Baltimore classification]] system is used to group viruses together based on their manner of [[messenger RNA]] (mRNA) synthesis and is often used alongside standard virus taxonomy, which is based on evolutionary history. DNA viruses constitute two Baltimore groups: Group I: double-stranded DNA viruses, and Group II: single-stranded DNA viruses. While Baltimore classification is chiefly based on [[Transcription (biology)|transcription]] of mRNA, viruses in each Baltimore group also typically share their manner of replication. Viruses in a Baltimore group do not necessarily share genetic relation or morphology.<ref name=lostroh11 >[[#reflostrohlostroh|Lostroh 2019]], pp.&nbsp;11–13</ref>

The first Baltimore group of DNA viruses are those 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 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.<ref name=dsdna >{{cite web|title=dsDNA templated transcription|url=https://viralzone.expasy.org/1942|website=ViralZone|publisher=Swiss Institute of Bioinformatics|accessdateaccess-date=24 September 2020}}</ref><ref name=rampersad66 >[[#reframpersadrampersad|Rampersad 2018]], p.&nbsp;66</ref><ref name=fermin36 >[[#refferminfermin|Fermin 2018]], pp.&nbsp;36–40</ref>

dsDNA viruses make use of several mechanisms to replicate their genome. Bidirectional replication, which is the typical form of [[DNA replication]] in eukaryotes,which is widely used. In bidirectionaltwo replication, aforks circularare genomeestablished is cleaved to separate the two strands, creatingat a fork from which replication oforigin bothsite strands progresses around the genome at the same time,and goingmove in two opposite directions untilof theeach opposite endother, is reachedwidely used.<ref name=bidi >{{cite web|title=dsDNA bidirectional replication|url=https://viralzone.expasy.org/1939|website=ViralZone|publisher=Swiss Institute of Bioinformatics|accessdateaccess-date=24 September 2020}}</ref> A rolling circle mechanism that produces linear strands while progressing in a loop around the circular genome is also used that likewise replicates both strands simultaneouslycommon.<ref name=dsdnarcr >{{cite web|title=dsDNA rolling circle replication|url=https://viralzone.expasy.org/2676|website=ViralZone|publisher=Swiss Institute of Bioinformatics|accessdateaccess-date=24 September 2020}}</ref><ref>{{cite Insteadjournal of|vauthors=Bernstein replicatingH, bothBernstein strandsC at|date=5 once,July 1973 |title=Circular and branched circular concatenates as possible intermediates in somebacteriophage T4 DNA replication |journal=J Mol Biol |volume=77 |issue=3 |pages=355–361 |doi=10.1016/0022-2836(73)90443-9 |pmid=4580243}}</ref> 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.<ref name=displace >{{cite web|title=DNA strand displacement replication|url=https://viralzone.expasy.org/1940|website=ViralZone|publisher=Swiss Institute of Bioinformatics|accessdateaccess-date=24 September 2020}}</ref> 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.<ref name=reptrans>{{cite web|title=Replicative transposition|url=https://viralzone.expasy.org/4017|website=ViralZone|publisher=Swiss Institute of Bioinformatics|accessdateaccess-date=24 September 2020}}</ref>

dsDNA viruses can be subdivided between those that replicate in the [[cell 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.<ref name=cann122 >[[#refcanncann|Cann 2015]], pp.&nbsp;122–127</ref> 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''.<ref name=duplo >{{cite web|vauthors=Koonin EV, Dolja VV, Krupovic M, Varsani A, Wolf YI, Yutin N, Zerbini M, Kuhn JH|title=Create a megataxonomic framework, filling all principal/primary taxonomic ranks, for dsDNA viruses encoding HK97-type major capsid proteins|url=https://talk.ictvonlineictv.orgglobal/ictv/proposals/2019.004G.zip|website=International Committee on Taxonomy of Viruses|accessdateaccess-date=24 September 2020|language=en|format=docx|date=18 October 2019}}</ref><ref name=vari >{{cite web|vauthors=Koonin EV, Dolja VV, Krupovic M, Varsani A, Wolf YI, Yutin N, Zerbini M, Kuhn JH|title=Create a megataxonomic framework, filling all principal taxonomic ranks, for DNA viruses encoding vertical jelly roll-type major capsid proteins|url=https://talk.ictvonlineictv.orgglobal/ictv/proposals/2019.003G.zip|website=International Committee on Taxonomy of Viruses|accessdateaccess-date=24 September 2020|language=en|format=docx|date=18 October 2019}}</ref>

The second Baltimore group of DNA viruses are those that have a single-stranded DNA genome. ssDNA viruses have the same manner of transcription as dsDNA viruses. However, because the genome is single-stranded, 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.<ref name=ssdna >{{cite web|title=ssDNA Rolling circle|url=https://viralzone.expasy.org/1941|website=ViralZone|publisher=Swiss Institute of Bioinformatics|accessdateaccess-date=24 September 2020}}</ref><ref name=hairpin >{{cite web|title=Rolling hairpin replication|url=https://viralzone.expasy.org/2656|website=ViralZone|publisher=Swiss Institute of Bioinformatics|accessdateaccess-date=24 September 2020}}</ref> Eukaryotic ssDNA viruses are replicated in the nucleus.<ref name=cann122 /><ref name=fermin40 >[[#refferminfermin|Fermin 2018]], pp.&nbsp;40–41</ref>

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 [[Ligation (molecular biology)|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.<ref name=ssdna /><ref name=rampersad61 >[[#reframpersadrampersad|Rampersad 2018]], pp.&nbsp;61–62</ref>

[[Parvovirus]]es contain linear ssDNA genomes that are replicated via [[rolling hairpin replication]] (RHR)., RHRwhich is similar to RCR. butParvovirus eachgenomes end of the linear genome contains anhave [[inverted repeatStem-loop|invertedhairpin terminal repeatloops]] inat aeach [[hairpinend loop]] structure. Afterof the genome hasthat beenrepeatedly repairedunfold byand arefold DNAduring polymerasereplication to form dsDNA,change the endonucleasedirection unbindsof theDNA hairpinsynthesis loops,to whichmove areback replicatedand with theforth rest ofalong the genome., Theproducing dsDNAnumerous genomecopies isof thenthe cleavedgenome in two,a andcontinuous theprocess. hairpinIndividual loopsgenomes atare boththen endsexcised offrom boththis strandsmolecule areby formedthe viral endonuclease. For parvoviruses, either the [[Sense (molecular biology)|positive or negative sense]] strand may be packaged into capsids, varying from virus to virus.<ref name=hairpinrampersad61 /><ref>{{cite namebook |vauthors=rampersad61Kerr J, Cotmore S, Bloom ME |date=25 November 2005 |title=Parvoviruses |publisher=CRC Press |pages=171–185 |isbn=9781444114782}}</ref>

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.<ref name=fermin40 /> Parvoviruses, as previously mentioned, may package either the positive or negative sense strand into virions.<ref name=hairpin /> Lastly, [[Bidensovirus|bidnavirus]]es package both the positive and negative linear strands.<ref name=fermin40 /><ref name=bidna >{{cite web|title=Bidnaviridae|url=https://viralzone.expasy.org/2957|website=ViralZone|publisher=Swiss Institute of Bioinformatics|accessdateaccess-date=24 September 2020}}</ref>

The [[International Committee on Taxonomy of Viruses]] (ICTV) oversees virus taxonomy and organizes viruses at the basal level at the rank of realm. Virus realms correspond to the rank of [[Domain (biology)|domain]] used for cellular life but differ in that viruses within a realm do not necessarily share [[common ancestry]], nor do the realms share common ancestry with each other. As such, each virus realm represents at least one instance of viruses coming into existence. Within each realm, viruses are grouped together based on shared characteristics that are [[highly conserved]] over time.<ref name=exec >{{cite journal|author=International Committee on Taxonomy of Viruses Executive Committee|date=May 2020|title=The New Scope of Virus Taxonomy: Partitioning the Virosphere Into 15 Hierarchical Ranks|url=https://www.nature.com/articles/s41564-020-0709-x|journal=Nat Microbiol|volume=5|issue=5|pages=668–674|doi=10.1038/s41564-020-0709-x|pmc=7186216|pmid=32341570|accessdate=24 September 2020}}</ref> Three DNA virus realms are recognized: ''Duplodnaviria'', ''Monodnaviria'', and ''Varidnaviria''.

[[File:Duplodnaviria_virion_morphologyDuplodnaviria virion morphology.jpg|thumb|Illustrated sample of ''Duplodnaviria'' virions]]

''Duplodnaviria'' is eithera monophyleticvery orancient polyphyletic andrealm, mayperhaps predatepredating the [[last universal common ancestor]] (LUCA) of cellular life. TheIts exactorigins originnot ofknown, thenor realmwhether it is notmonophyletic known,or butpolyphyletic. A characteristic feature is the HK97-fold found in the MCP of all members, which is, found outside the realm, only found in [[encapsulin]]s, a type of nanocompartment found in bacteria,: although thethis relation between ''Duplodnaviria'' and encapsulins is not fully understood.<ref name=duplo /><ref name=krupovic >{{cite journal|vauthors=Krupovic M, Koonin EV|date=21 March 2017|title=Multiple origins of viral capsid proteins from cellular ancestors|journal=Proc Natl Acad Sci U S A|volume=114|issue=12|pages=E2401–E2410|doi=10.1073/pnas.1621061114|pmc=5373398|pmid=28265094|bibcode=2017PNAS..114E2401K |doi-access=free}}</ref><ref name=luca >{{cite journal|last1=Krupovic|first1=M|last2=Dolja|first2=VV|last3=Koonin|first3=EV|title=The LUCA and its complex virome.|journal=Nat Rev Microbiol|date=14 July 2020|volume=18|issue=11|pages=661–670|doi=10.1038/s41579-020-0408-x|pmid=32665595|s2cid=220516514|url=https://bpp.oregonstate.edu/sites/agscid7/files/bpp/attachments/lucavirome2020.pdf |accessdatearchive-url=https://web.archive.org/web/20201027183841/https://bpp.oregonstate.edu/sites/agscid7/files/bpp/attachments/lucavirome2020.pdf |archive-date=2020-10-27 |url-status=live|access-date=24 September 2020}}</ref>

The relation between caudoviruses and herpesviruses is notalso certain, asuncertain: they may either share a common ancestor or herpesviruses may be a divergent clade from withinthe realm ''Caudovirales''. A common trait among duplodnaviruses is that they cause latent infections without replication while still being able to replicate in the future.<ref>{{cite journal|vauthors=Weidner-Glunde M, Kruminis-Kaszkiel E, Savanagoudar M|date=February 2020|title=Herpesviral Latency—Common Themes|journal=Pathogens|volume=9|issue=2|pages=125|doi=10.3390/pathogens9020125|pmc=7167855|pmid=32075270|doi-access=free}}</ref><ref>{{cite web|title=Virus latency|url=https://viralzone.expasy.org/3970|website=ViralZone|publisher=Swiss Institute of Bioinformatics|accessdateaccess-date=24 September 2020}}</ref> Tailed bacteriophages are ubiquitous worldwide,<ref>{{cite journal|vauthors=Andrade-Martínez JS, Moreno-Gallego JL, Reyes A|date=August 2019|title=Defining a Core Genome for the Herpesvirales and Exploring their Evolutionary Relationship with the Caudovirales|url=https://www.nature.com/articles/s41598-019-47742-z.pdf?proof=true|journal=Sci Rep|volume=9|issue=1|pages=11342 |doi=10.1038/s41598-019-47742-z|pmc=6683198|pmid=31383901|bibcode=2019NatSR...911342A|accessdate=24 September 2020}}</ref> important in marine ecology,<ref>{{cite journal|vauthors=Wilhelm SW, Suttle CA|date=October 1999|title=Viruses and Nutrient Cycles in the Sea: Viruses play critical roles in the structure and function of aquatic food webs|url=https://academic.oup.com/bioscience/article/49/10/781/222807|journal=BioScience|volume=49|issue=10|pages=781–788|doi=10.2307/1313569|jstor=1313569|pmc=|pmid=|accessdate=24 September 2020|doi-access=free}}</ref> and the subject of much research.<ref>{{cite journal|vauthors=Keen EC|date=January 2015|title=A century of phage research: Bacteriophages and the shaping of modern biology|journal=BioEssays|volume=37|issue=1|pages=6–9|doi=10.1002/bies.201400152|pmc=4418462|pmid=25521633}}</ref> Herpesviruses are known to cause a variety of epithelial diseases, including [[herpes simplex]], [[chickenpox]] and [[shingles]], and [[Kaposi's sarcoma]].<ref>{{cite journal|vauthors=Kukhanova MK, Korovina AN, Kochetkov SN|date=December 2014|title=Human herpes simplex virus: life cycle and development of inhibitors|journal=Biochemistry (Mosc)|volume=79|issue=13|pages=1635–1652|doi=10.1134/S0006297914130124|pmc=|pmid=25749169|s2cid=7414402}}</ref><ref>{{cite journal|vauthors=Gershon AA, Breuer J, Cohen JI, Cohrs RJ, Gershon MD, Gilden D, Grose C, Hambleton S, Kennedy PG, Oxman MN, Seward JF, Yamanishi K|date=2 July 2015|title=Varicella zoster virus infection|url=https://www.nature.com/articles/nrdp201516|journal=Nat Rev Dis Primers|volume=1|issue=|pages=15016|doi=10.1038/nrdp.2015.16|pmc=5381807|pmid=27188665|accessdate=24 September 2020}}</ref><ref>{{cite journal|vauthors=O'Leary JJ, Kennedy MM, McGee JO|date=February 1997|title=Kaposi's sarcoma associated herpes virus (KSHV/HHV 8): epidemiology, molecular biology and tissue distribution|journal=Mol Pathol|volume=50|issue=1|pages=4–8|doi=10.1136/mp.50.1.4|pmc=379571|pmid=9208806}}</ref>

''[[Monodnaviria]]'' contains ssDNA viruses that encode an [[endonuclease]] of the HUH superfamily that initiates [[rolling circle replication]] and all other viruses descended from such viruses. The prototypical members of the realm are called CRESS-DNA viruses and have circular ssDNA genomes. ssDNA viruses with linear genomes are descended from them, and in turn some dsDNA viruses with circular genomes are descended from linear ssDNA viruses.<ref name=mono />

Viruses in ''Monodnaviria'' appear to have emerged on multiple occasions from archaeal and bacterial [[plasmid]]s, a type of extra-chromosomal DNA molecule that self-replicates inside its host. The kingdom ''Shotokuvirae'' in the realm likely emerged from recombination events that merged the DNA of these plasmids and complementary DNA encoding the capsid proteins of RNA viruses.<ref name=mono /><ref>{{cite journal|vauthors=Kazlauskas D, Varsani A, Koonin EV, Krupovic M|date=31 July 2019|title=Multiple Origins of Prokaryotic and Eukaryotic Single-Stranded DNA Viruses From Bacterial and Archaeal Plasmids|url=https://www.nature.com/articles/s41467-019-11433-0|journal=Nat Commun|volume=10|issue=1|pages=3425|doi=10.1038/s41467-019-11433-0|pmc=6668415|pmid=31366885|bibcode=2019NatCo..10.3425K|accessdate=24 September 2020}}</ref>

CRESS-DNA viruses include three kingdoms that infect prokaryotes: ''[[Loebvirae]]'', ''[[Sangervirae]]'', and ''[[Trapavirae]]''. The kingdom ''[[Shotokuvirae]]'' contains eukaryotic CRESS-DNA viruses and the atypical members of ''Monodnaviria''.<ref name=mono /> Eukaryotic monodnaviruses are associated with many diseases, and they include [[papillomavirus]]es and [[polyomavirus]]es, which cause many cancers,<ref>{{cite web|title=Papillomaviridae|url=https://viralzone.expasy.org/5|website=ViralZone|publisher=Swiss Institute of Bioinformatics|accessdateaccess-date=24 September 2020}}</ref><ref>{{cite web|title=Polyomaviridae|url=https://viralzone.expasy.org/148|website=ViralZone|publisher=Swiss Institute of Bioinformatics|accessdateaccess-date=24 September 2020}}</ref> and [[geminivirus]]es, which infect many economically important crops.<ref>{{cite journal|vauthors=Malathi VG, Renuka Devi P|date=March 2019|title=ssDNA Viruses: Key Players in Global Virome|url=|journal=Virusdisease|volume=30|issue=1|pages=3–12|doi=10.1007/s13337-019-00519-4|pmc=6517461|pmid=31143827|accessdate=}}</ref>

Marine viruses in ''Varidnaviria'' are ubiquitous worldwide and, like tailed bacteriophages, play an important role in marine ecology.<ref>{{cite journal|vauthors=Kauffman KM, Hussain FA, Yang J, Arevalo P, Brown JM, Chang WK, VanInsberghe D, Elsherbini J, Sharma RS, Cutler MB, Kelly L, Polz MF|date=1 February 2018|title=A Major Lineage of Non-Tailed dsDNA Viruses as Unrecognized Killers of Marine Bacteria|url=|journal=Nature|volume=554|issue=7690|pages=118–122|doi=10.1038/nature25474|pmc=|pmid=29364876|bibcode=2018Natur.554..118K|s2cid=4462007}}</ref> Most identified eukaryotic DNA viruses belong to the realm.<ref name=krupovic2015 >{{cite journal|vauthors=Krupovic M, Koonin EV|date=February 2015|title=Polintons: a hotbed of eukaryotic virus, transposon and plasmid evolution|url=|journal=Nat Rev Microbiol|volume=13|issue=2|pages=105–115|doi=10.1038/nrmicro3389|pmc=5898198|pmid=25534808|accessdate=}}</ref> NotablyNotable disease-causing viruses in ''Varidnaviria'' include [[adenovirus]]es, [[poxvirus]]es, and the [[African swine fever virus]].<ref name=ictv >{{cite web|url=https://talk.ictvonlineictv.orgglobal/taxonomy/|title=Virus Taxonomy: 2019 Release|last=|first=|date=|website=International Committee on Taxonomy of Viruses|publisher=International Committee on Taxonomy of Viruses|accessdateaccess-date=24 September 2020|quote=}}</ref> Poxviruses have been highly prominent in the history of modern medicine, especially ''Variola virus'', which caused [[smallpox]].<ref>{{cite journal|vauthors=Meyer H, Ehmann R, Smith GL|date=February 2020|title=Smallpox in the Post-Eradication Era|url=|journal=Viruses|volume=12|issue=2|pages=138|doi=10.3390/v12020138|pmc=7077202|pmid=31991671|accessdatedoi-access=free}}</ref> Many varidnaviruses are able tocan become endogenized in their host's genome, and; a peculiar example of this are [[virophage]]s, which conferafter protectioninfecting fora theirhost, can hostsprotect the host against [[giant virus]]es during infection.<ref name=krupovic2015 />

===By Baltimore groupclassification===

* All viruses in ''Duplodnaviria'' are dsDNA viruses.<ref name=duplo />

* In ''Monodnaviria'', members of the class ''[[Papovaviricetes]]'' are dsDNA viruses.<ref name=mono >{{cite web|vauthors=Koonin EV, Dolja VV, Krupovic M, Varsani A, Wolf YI, Yutin N, Zerbini M, Kuhn JH|title=Create a megataxonomic framework, filling all principal taxonomic ranks, for ssDNA viruses|url=https://talk.ictvonlineictv.orgglobal/ictv/proposals/2019.005G.zip|website=International Committee on Taxonomy of Viruses|accessdateaccess-date=24 September 2020|language=en|format=docx|date=18 October 2019}}</ref>

* All viruses in ''Varidnaviria'' are dsDNA viruses.<ref name=vari />

* The following taxa that are unassigned to a realm exclusively contain dsDNA viruses:<ref name=vari />

** Orders: ''[[Ligamenvirales]]''

** Families: ''[[Ampullaviridae]]'', ''[[Baculoviridae]]'', ''[[Bicaudaviridae]]'', ''[[Clavaviridae]]'', ''[[Fuselloviridae]]'', ''[[Globuloviridae]]'', ''[[Guttaviridae]]'', ''[[Halspiviridae]]'', ''[[Hytrosaviridae]]'', ''[[Nimaviridae]]'', ''[[Nudiviridae]]'', ''[[Ovaliviridae]]'', ''[[Plasmaviridae]]'', ''[[Polydnaviridae]]'', ''[[Portogloboviridae]]'', ''[[Thaspiviridae]]'', ''[[Tristromaviridae]]''

** Genera: ''[[Dinodnavirus]]'', ''[[Rhizidiovirus]]''

* In ''Monodnaviria'', all members except viruses in ''Papovaviricetes'' are ssDNA viruses.<ref name=mono />

* The unassigned families ''[[Anelloviridae]]'' and ''[[Spiraviridae]]'' are ssDNA virus families.<ref name=mono />

* Viruses in the family ''[[Finnlakeviridae]]'' contain ssDNA genomes. ''Finnlakeviridae'' is unassigned to a realm but is a proposed member of ''Varidnaviria''.<ref name=vari />

<span* id="lostroh" class="citation" >{{cite book|last=Lostroh|first=P.|author-link=|year=2019|title=Molecular and Cellular Biology of Viruses|url=https://books.google.com/books?id=BcmWDwAAQBAJ&q=baltimore+classification&pg=PT58|location=|publisher=Garland Science|page=|isbn=978-0429664304|accessdateaccess-date=24 September 2020|ref=lostroh}}</span>