View source for Cytomegalovirus

{{Short description|Genus of viruses}}
{{Use dmy dates|date=April 2017}}
{{Virusbox
| image             = Cytomegalovirus 01.jpg
| image_alt         = Typical "owl eye" intranuclear inclusion indicating CMV infection of a lung pneumocyte
| image_caption     = Typical "owl eye" intranuclear [[Inclusion bodies|inclusion]] indicating CMV infection of a lung [[pneumocyte]]<ref>{{cite journal | vauthors = Mattes FM, McLaughlin JE, Emery VC, Clark DA, Griffiths PD | title = Histopathological detection of owl's eye inclusions is still specific for cytomegalovirus in the era of human herpesviruses 6 and 7 | journal = Journal of Clinical Pathology | volume = 53 | issue = 8 | pages = 612–614 | date = August 2000 | pmid = 11002765 | pmc = 1762915 | doi = 10.1136/jcp.53.8.612 }}</ref>
| taxon             = Cytomegalovirus
| synonyms          =
* ''Human cytomegalovirus group''
| synonyms_ref      = <ref>{{cite journal | vauthors = Francki RI, Fauquet CM, Knudson DL, Brown | title = Classification and nomenclature of viruses. Fifth Report of the International Committee on Taxonomy of Viruses. | journal = Arch. Virol. | date = 1991 | page = 107 | url = https://ictv.global/ictv/proposals/ICTV%205th%20Report.pdf }}</ref>
| subdivision_ranks = Species
| subdivision       = See text
}}

'''''Cytomegalovirus''''' ('''CMV''') (from ''cyto-'' 'cell' via [[Ancient Greek|Greek]] {{lang|grc|κύτος}} {{transliteration|grc|kútos}}- 'container' + {{lang|grc|μέγας}} {{transliteration|grc|mégas}} 'big, megalo-' + -''virus'' via [[Latin]] {{lang|la|vīrus}} 'poison') is a genus of [[virus]]es in the order ''[[Herpesvirales]]'', in the family ''[[Herpesviridae]]'',<ref>{{cite journal | vauthors = Anshu A, Tan D, Chee SP, Mehta JS, Htoon HM | title = Interventions for the management of CMV-associated anterior segment inflammation | journal = The Cochrane Database of Systematic Reviews | volume = 2017 | article-number = CD011908 | date = August 2017 | issue = 8 | pmid = 28838031 | pmc = 6483705 | doi = 10.1002/14651858.cd011908.pub2 }}</ref> in the subfamily ''[[Betaherpesvirinae]]''. [[Human]]s and other [[primate]]s serve as natural [[host (biology)|hosts]]. The 11 species in this genus include ''[[human betaherpesvirus 5]]'' (HCMV, human cytomegalovirus, HHV-5), which is the [[species]] that infects humans. Diseases associated with HHV-5 include [[infectious mononucleosis|mononucleosis]] and [[pneumonia]],<ref name=ViralZone>{{cite web|title=Viral Zone|url=http://viralzone.expasy.org/all_by_species/180.html|publisher=ExPASy|access-date=15 June 2015}}</ref><ref name=ICTV>{{cite web |title=Virus Taxonomy: 2022 Release |url=https://ictv.global/taxonomy |publisher=International Committee on Taxonomy of Viruses (ICTV) |date=March 2023 |access-date=16 September 2022}}</ref> and [[Congenital cytomegalovirus infection|congenital CMV]] in infants can lead to variety of birth defects, including those involving the eyes, ears, liver, and spleen.<ref>{{Cite web |date=2017-10-23 |title=Cytomegalovirus (CMV) |url=https://www.nhs.uk/conditions/cytomegalovirus-cmv/ |access-date=2025-10-30 |website=nhs.uk |language=en}}</ref>

In the [[medical literature]], most mentions of CMV without further specification refer implicitly to human CMV. Human CMV is the most studied of all cytomegaloviruses.<ref name=Sherris>{{cite book | veditors = Ryan KJ, Ray CG | title = Sherris Medical Microbiology | edition = 4th | pages = 556; 566–569 | publisher = McGraw Hill | year = 2004 | isbn = 978-0-8385-8529-0 }}</ref>

[[MX2|MX2/MXB]] protein was identified as a restriction factor for herpesviruses, which acts at a very early stage of the replication cycle and MX2/MXB restriction of herpesvirus requires [[GTPase]] activity.<ref name="Staeheli_2018">{{cite journal | vauthors = Staeheli P, Haller O | title = Human MX2/MxB: a Potent Interferon-Induced Postentry Inhibitor of Herpesviruses and HIV-1 | journal = Journal of Virology | volume = 92 | issue = 24 | pages = | date = December 2018 | pmid = 30258007 | pmc = 6258936 | doi = 10.1128/JVI.00709-18 }}</ref>

== Taxonomy ==
Within the ''[[Herpesviridae]]'', CMV belongs to the ''[[Betaherpesvirinae]]'' subfamily, which also includes the genera ''[[Muromegalovirus]]'' and ''[[Roseolovirus]]'' ([[human herpesvirus 6]] and [[human herpesvirus 7]]).<ref name="isbn0-521-82714-0">{{cite book | vauthors = Koichi Y, Arvin AM, Campadelli-Fiume G, Mocarski E, Patrick M, Roizman B, Whitley R |title=Human Herpesviruses: Biology, Therapy, and Immunoprophylaxis |publisher=Cambridge University Press |location=Cambridge, UK |year=2007 |isbn=978-0-521-82714-0 }}</ref> It is also related to other herpesviruses within the ''[[Alphaherpesvirinae]]'' subfamily, which includes [[herpes simplex virus]]es 1 and 2 and [[varicella-zoster virus]], and the ''[[Gammaherpesvirinae]]'' subfamily, which includes [[Epstein–Barr virus]] and [[Kaposi's sarcoma-associated herpesvirus]].<ref name="Sherris" />

Several species of ''Cytomegalovirus'' have been identified and classified for different [[mammal]]s.<ref name="isbn0-521-82714-0"/> The most studied is ''Human cytomegalovirus'' (HCMV), which is also known as ''Human betaherpesvirus 5'' (HHV-5). Other primate CMV species include ''Chimpanzee cytomegalovirus'' (CCMV) that infects [[Common chimpanzee|chimpanzee]]s and [[orangutan]]s, and ''Simian cytomegalovirus'' (SCCMV) and ''Rhesus cytomegalovirus'' (RhCMV) that infect [[macaque]]s; CCMV is known as both ''Panine beta herpesvirus 2'' (PaHV-2) and ''Pongine betaherpesvirus 4'' (PoHV-4).<ref>{{cite web|url=https://www.uniprot.org/taxonomy/188763|title=Panine betaherpesvirus 2 (Chimpanzee cytomegalovirus)|website=www.uniprot.org|access-date=13 March 2019}}</ref> SCCMV is called ''cercopithecine betaherpesvirus 5'' (CeHV-5)<ref>{{cite web|url=https://www.uniprot.org/taxonomy/50292|title=Simian cytomegalovirus (strain Colburn)|website=www.uniprot.org|access-date=13 March 2019}}</ref> and RhCMV, ''Cercopithecine betaherpesvirus 8'' (CeHV-8).<ref>{{cite web|url=https://www.uniprot.org/taxonomy/47929|title=Macacine betaherpesvirus 3 (Rhesus cytomegalovirus)|website=www.uniprot.org|access-date=13 March 2019}}</ref> A further two viruses found in the [[night monkey]] are tentatively placed in the genus ''Cytomegalovirus'', and are called ''Herpesvirus aotus 1'' and ''Herpesvirus aotus 3''. Rodents also have viruses previously called cytomegaloviruses that are now reclassified under the genus ''[[Muromegalovirus]]''; this genus contains ''Mouse cytomegalovirus'' (MCMV) is also known as ''Murid betaherpesvirus 1'' (MuHV-1) and the closely related ''Murid betaherpesvirus 2'' (MuHV-2) that is found in [[rat]]s.<ref>{{cite web|url=http://www.ncbi.nlm.nih.gov/nuccore/NC_004065.1|title=Murid herpesvirus 1, complete genome|date=13 August 2018|access-date=13 March 2019|via=NCBI Nucleotide}}</ref>

=== Species ===
The following 11 species are assigned to the genus in ICTV 2022:<ref name=ICTV />
{{div col|colwidth=20em}}
* ''[[Aotine betaherpesvirus 1|Cytomegalovirus aotinebeta1]]''
* ''[[Cebine betaherpesvirus 1|Cytomegalovirus cebinebeta1]]''
* ''[[Cercopithecine betaherpesvirus 5|Cytomegalovirus cercopithecinebeta5]]''
* ''[[Human betaherpesvirus 5|Cytomegalovirus humanbeta5]]''
* ''[[Macacine betaherpesvirus 3|Cytomegalovirus macacinebeta3]]''
* ''[[Macacine betaherpesvirus 8|Cytomegalovirus macacinebeta8]]''
* ''[[Mandrilline betaherpesvirus 1|Cytomegalovirus mandrillinebeta1]]''
* ''[[Panine betaherpesvirus 2|Cytomegalovirus paninebeta2]]''
* ''[[Papiine betaherpesvirus 3|Cytomegalovirus papiinebeta3]]''
* ''[[Papiine betaherpesvirus 4|Cytomegalovirus papiinebeta4]]''
* ''[[Saimiriine betaherpesvirus 4|Cytomegalovirus saimiriinebeta4]]''
{{div col end}}

== Structure ==
[[File:CMVschema.svg|thumb|right|Schematic of a ''Cytomegalovirus'']]
Viruses in ''Cytomegalovirus'' are enveloped, with icosahedral, spherical to pleomorphic, and round geometries, and T=16 symmetry. The diameter is around 150–200&nbsp;nm. Genomes are linear and nonsegmented, around 200 kb in length.<ref name=ViralZone />

{| class="wikitable sortable" style="text-align:center"
|-
! Genus !! Structure || Symmetry !! Capsid !! Genomic arrangement !! Genomic segmentation
|-
|''Cytomegalovirus''||Spherical pleomorphic||T=16||Enveloped||Linear||Monopartite
|}

== Genome ==
[[File:HCMV genome.png|thumb|Class E genome of HCMV. The unique long and unique short regions are indicated as UL and US. Repeat regions are indicated as a, b and c sequences, where primes designate inverted orientations. Sequences ''ab'' and ''b′a′'' correspond to the terminal/internal repeat long (TRL/IRL); sequences ''a′c′'' and ''ca'' correspond to the internal/terminal repeat short (IRS/TRS). '''Top''': typical genome arrangement of wild-type strains; '''bottom''': genome arrangement of strain AD169, a laboratory-adapted strain. Genome rearrangements that have occurred during extensive passaging are indicated in red between the wild-type and laboratory-adapted configurations.<ref name=":0" />|alt=|400px]]

Herpesviruses have some of the largest genomes among human viruses, often encoding hundreds of proteins. For instance, the double‑stranded DNA (dsDNA) [[genome]] of wild-type HCMV strains has a size of around 235 kb and encodes at least 208 proteins. It is thus longer than all other human herpesviruses and one of the longest genomes of all human viruses in general. It has the characteristic herpesvirus class E genome architecture, consisting of two unique regions (unique long UL and unique short US), both flanked by a pair of inverted repeats (terminal/internal repeat long TRL/IRL and internal/terminal repeat short IRS/TRS). Both sets of repeats share a region of a few hundred bps, the so-called "a sequence"; the other regions of the repeats are sometimes referred to as "b sequence" and "c sequence".<ref name=":0">{{cite journal | vauthors = Sijmons S, Van Ranst M, Maes P | title = Genomic and functional characteristics of human cytomegalovirus revealed by next-generation sequencing | journal = Viruses | volume = 6 | issue = 3 | pages = 1049–1072 | date = March 2014 | pmid = 24603756 | pmc = 3970138 | doi = 10.3390/v6031049 | doi-access = free }}</ref>

== {{anchor|Lifecycle}}Life cycle ==
Viral replication is nuclear and [[Lysogenic cycle|lysogenic.]] Entry into the host cell is achieved by attachment of the viral [[glycoproteins]] to host receptors, which mediates [[endocytosis]]. [[DNA replication|Replication]] follows the dsDNA bidirectional replication model. [[Transcription (genetics)#Elongation|DNA templated transcription]], with some [[alternative splicing]] mechanism is the method of transcription. [[Translation (biology)|Translation]] takes place by [[leaky scanning]]. The virus exits the host cell by nuclear egress and [[Viral shedding#Via budding|budding.]] Humans and monkeys serve as the natural hosts. Transmission routes are dependent on coming into contact with bodily fluids (such as saliva, urine, and genital secretions) from an infected individual.<ref name=ViralZone /><ref>{{cite journal | vauthors = Cannon MJ, Hyde TB, Schmid DS | title = Review of cytomegalovirus shedding in bodily fluids and relevance to congenital cytomegalovirus infection | journal = Reviews in Medical Virology | volume = 21 | issue = 4 | pages = 240–255 | date = July 2011 | pmid = 21674676 | pmc = 4494736 | doi = 10.1002/rmv.695 }}</ref>

{| class="wikitable sortable" style="text-align:center"
|-
! Genus !! Host details !! Tissue tropism !! Entry details !! Release details !! Replication site !! Assembly site !! Transmission
|-
|''Cytomegalovirus''||humans; monkeys||Epithelial mucosa||Glycoproteins||Budding||Nucleus||Nucleus||Urine; saliva; congenital
|}

All [[human herpesviruses|herpesviruses]] share a characteristic ability to remain [[Virus latency|latent]] within the body over long periods. Although they may be found throughout the body, CMV infections are frequently associated with the [[salivary gland]]s in humans and other [[mammal]]s.<ref name="isbn0-521-82714-0"/>

==Genetic engineering==
The CMV promoter is commonly included in [[Vector (molecular biology)|vectors]] used in [[genetic engineering]] work conducted in [[mammal]]ian cells, as it is a strong [[promoter (genetics)|promoter]] and drives constitutive expression of genes under its control.<ref>{{cite web | first = Kendall | last = Morgan | name-list-style = vanc | work = Addgene Blog | date = 3 April 2014 | url = http://blog.addgene.org/plasmids-101-the-promoter-region | title = Plasmids 101: The Promoter Region – Let's Go! }}</ref>

== History ==
''Cytomegalovirus'' was first observed by German pathologist [[Hugo Ribbert]] in 1881 when he noticed enlarged cells with enlarged nuclei present in the cells of an infant.<ref>{{Cite book | veditors = Reddehase MJ, Lemmermann N | page = xxiv |chapter=Preface |title=Cytomegaloviruses: Molecular Biology and Immunology |publisher=Horizon Scientific Press |year=2006 |isbn=9781904455028 }}</ref> Years later, between 1956 and 1957, [[Thomas Huckle Weller]] together with Smith and Rowe independently isolated the virus, known thereafter as "cytomegalovirus".<ref>{{cite journal | vauthors = Craig JM, Macauley JC, Weller TH, Wirth P | title = Isolation of intranuclear inclusion producing agents from infants with illnesses resembling cytomegalic inclusion disease | journal = Proceedings of the Society for Experimental Biology and Medicine | volume = 94 | issue = 1 | pages = 4–12 | date = January 1957 | pmid = 13400856 | doi = 10.3181/00379727-94-22841 | s2cid = 29263626 }}</ref> In 1990, the first draft of human cytomegalovirus genome was published,<ref>{{cite book | vauthors = Chee MS, Bankier AT, Beck S, Bohni R, Brown CM, Cerny R, Horsnell T, Hutchison CA, Kouzarides T, Martignetti JA | chapter = Analysis of the Protein-Coding Content of the Sequence of Human Cytomegalovirus Strain AD169 | title = Cytomegaloviruses | display-authors = 6 | volume = 154 | pages = 125–169 | date = 1990 | pmid = 2161319 | doi = 10.1007/978-3-642-74980-3_6 | publisher = Springer Berlin Heidelberg | isbn = 978-3-642-74982-7 | series = Current Topics in Microbiology and Immunology }}</ref> the biggest contiguous genome sequenced at that time.<ref>{{cite journal | vauthors = Martí-Carreras J, Maes P | title = Human cytomegalovirus genomics and transcriptomics through the lens of next-generation sequencing: revision and future challenges | journal = Virus Genes | volume = 55 | issue = 2 | pages = 138–164 | date = April 2019 | pmid = 30604286 | pmc = 6458973 | doi = 10.1007/s11262-018-1627-3 }}</ref>

== See also ==
{{Portal|Viruses}}
* [[CMV polyradiculomyelopathy]]
* [[Human betaherpesvirus 5|Human cytomegalovirus]]

== References ==
{{Reflist}}

== External links ==
{{Commons category}}
{{Wikispecies}}
* [http://ictvonline.org/virusTaxonomy.asp ICTV]

{{Medical resources
|   ICD10       = {{ICD10|B|25||b|25}}
|   ICD9        = {{ICD9|078.5}}
|   MedlinePlus = 000568
|   MeshID      = D003586
}}

{{Herpesvirales}}
{{Baltimore classification}}
{{Viral diseases}}
{{Diseases of maternal transmission}}
{{Taxonbar|from=Q6946}}
{{Authority control}}

[[Category:Viral diseases]]
[[Category:Betaherpesvirinae]]
[[Category:Virus genera]]