| Cytomegalovirus | |
|---|---|
 | |
| Typical "owl eye" intranuclearinclusion indicating CMV infection of a lungpneumocyte[1] | |
Virus classification | |
| (unranked): | Virus |
| Realm: | Duplodnaviria |
| Kingdom: | Heunggongvirae |
| Phylum: | Peploviricota |
| Class: | Herviviricetes |
| Order: | Herpesvirales |
| Family: | Orthoherpesviridae |
| Subfamily: | Betaherpesvirinae |
| Genus: | Cytomegalovirus |
| Species | |
See text | |
| Synonyms[2] | |
| |
Cytomegalovirus (CMV) (fromcyto- 'cell' viaGreekκύτοςkútos- 'container' +μέγαςmégas 'big, megalo-' + -virus viaLatinvīrus 'poison') is a genus ofviruses in the orderHerpesvirales, in the familyHerpesviridae,[3] in the subfamilyBetaherpesvirinae.Humans and otherprimates serve as naturalhosts. The 11 species in this genus includehuman betaherpesvirus 5 (HCMV, human cytomegalovirus, HHV-5), which is thespecies that infects humans. Diseases associated with HHV-5 includemononucleosis andpneumonia,[4][5] andcongenital CMV in infants can lead to variety of birth defects, including those involving the eyes, ears, liver, and spleen.[6]
In themedical literature, most mentions of CMV without further specification refer implicitly to human CMV. Human CMV is the most studied of all cytomegaloviruses.[7]
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 requiresGTPase activity.[8]
Within theHerpesviridae, CMV belongs to theBetaherpesvirinae subfamily, which also includes the generaMuromegalovirus andRoseolovirus (human herpesvirus 6 andhuman herpesvirus 7).[9] It is also related to other herpesviruses within theAlphaherpesvirinae subfamily, which includesherpes simplex viruses 1 and 2 andvaricella-zoster virus, and theGammaherpesvirinae subfamily, which includesEpstein–Barr virus andKaposi's sarcoma-associated herpesvirus.[7]
Several species ofCytomegalovirus have been identified and classified for differentmammals.[9] The most studied isHuman cytomegalovirus (HCMV), which is also known asHuman betaherpesvirus 5 (HHV-5). Other primate CMV species includeChimpanzee cytomegalovirus (CCMV) that infectschimpanzees andorangutans, andSimian cytomegalovirus (SCCMV) andRhesus cytomegalovirus (RhCMV) that infectmacaques; CCMV is known as bothPanine beta herpesvirus 2 (PaHV-2) andPongine betaherpesvirus 4 (PoHV-4).[10] SCCMV is calledcercopithecine betaherpesvirus 5 (CeHV-5)[11] and RhCMV,Cercopithecine betaherpesvirus 8 (CeHV-8).[12] A further two viruses found in thenight monkey are tentatively placed in the genusCytomegalovirus, and are calledHerpesvirus aotus 1 andHerpesvirus aotus 3. Rodents also have viruses previously called cytomegaloviruses that are now reclassified under the genusMuromegalovirus; this genus containsMouse cytomegalovirus (MCMV) is also known asMurid betaherpesvirus 1 (MuHV-1) and the closely relatedMurid betaherpesvirus 2 (MuHV-2) that is found inrats.[13]
The following 11 species are assigned to the genus in ICTV 2022:[5]
Viruses inCytomegalovirus are enveloped, with icosahedral, spherical to pleomorphic, and round geometries, and T=16 symmetry. The diameter is around 150–200 nm. Genomes are linear and nonsegmented, around 200 kb in length.[4]
| Genus | Structure | Symmetry | Capsid | Genomic arrangement | Genomic segmentation |
|---|---|---|---|---|---|
| Cytomegalovirus | Spherical pleomorphic | T=16 | Enveloped | Linear | Monopartite |
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".[14]
Viral replication is nuclear andlysogenic. Entry into the host cell is achieved by attachment of the viralglycoproteins to host receptors, which mediatesendocytosis.Replication follows the dsDNA bidirectional replication model.DNA templated transcription, with somealternative splicing mechanism is the method of transcription.Translation takes place byleaky scanning. The virus exits the host cell by nuclear egress andbudding. 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.[4][15]
| 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 |
Allherpesviruses share a characteristic ability to remainlatent within the body over long periods. Although they may be found throughout the body, CMV infections are frequently associated with thesalivary glands in humans and othermammals.[9]
The CMV promoter is commonly included invectors used ingenetic engineering work conducted inmammalian cells, as it is a strongpromoter and drives constitutive expression of genes under its control.[16]
Cytomegalovirus was first observed by German pathologistHugo Ribbert in 1881 when he noticed enlarged cells with enlarged nuclei present in the cells of an infant.[17] Years later, between 1956 and 1957,Thomas Huckle Weller together with Smith and Rowe independently isolated the virus, known thereafter as "cytomegalovirus".[18] In 1990, the first draft of human cytomegalovirus genome was published,[19] the biggest contiguous genome sequenced at that time.[20]
