Cytomegalovirus

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Cytomegalovirus
Typical "owl eye" intranuclear inclusion indicating CMV infection of a lung pneumocyte
Typical "owl eye" intranuclearinclusion indicating CMV infection of a lungpneumocyte[1]
Virus classificatione
(unranked):Virus
Realm:Duplodnaviria
Kingdom:Heunggongvirae
Phylum:Peploviricota
Class:Herviviricetes
Order:Herpesvirales
Family:Orthoherpesviridae
Subfamily:Betaherpesvirinae
Genus:Cytomegalovirus
Species

See text

Synonyms[2]
  • Human cytomegalovirus group

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] In themedical literature, most mentions of CMV without further specification refer implicitly to human CMV. Human CMV is the most studied of all cytomegaloviruses.[6]

MX2/MXB 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.[7]

Contents

Taxonomy

Within theHerpesviridae, CMV belongs to theBetaherpesvirinae subfamily, which also includes the generaMuromegalovirus andRoseolovirus (human herpesvirus 6 andhuman betaherpesvirus 7).[8] 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.[6]

Several species ofCytomegalovirus have been identified and classified for differentmammals.[8] 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).[9] SCCMV is calledcercopithecine betaherpesvirus 5 (CeHV-5)[10] and RhCMV,Cercopithecine betaherpesvirus 8 (CeHV-8).[11] 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.[12]

Species

The genus consists of these 11 species:[5]

Structure

Schematic of aCytomegalovirus

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]

GenusStructureSymmetryCapsidGenomic arrangementGenomic segmentation
CytomegalovirusSpherical pleomorphicT=16EnvelopedLinearMonopartite

Genome

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. Sequencesab andb′a′ correspond to the terminal/internal repeat long (TRL/IRL); sequencesa′c′ andca 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.[13]

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".[13]

Life cycle

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 bynuclear egressArchived 5 May 2017 at theWayback Machine, 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][14]

GenusHost detailsTissue tropismEntry detailsRelease detailsReplication siteAssembly siteTransmission
Cytomegalovirushumans; monkeysEpithelial mucosaGlycoproteinsBuddingNucleusNucleusUrine; 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.[8]

Genetic engineering

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.[15]

History

Cytomegalovirus shows characteristic cytoplasmic inclusions

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.[16]

Years later, between 1956 and 1957,Thomas Huckle Weller together with Smith and Rowe independently isolated the virus, known thereafter as "cytomegalovirus".[17]

In 1990, the first draft of human cytomegalovirus genome was published,[18] the biggest contiguous genome sequenced at that time.[19]

See also

    References

    1. Mattes FM, McLaughlin JE, Emery VC, Clark DA, Griffiths PD (August 2000)."Histopathological detection of owl's eye inclusions is still specific for cytomegalovirus in the era of human herpesviruses 6 and 7".Journal of Clinical Pathology.53 (8): 612–4.doi:10.1136/jcp.53.8.612.PMC 1762915.PMID 11002765.
    2. Francki RI, Fauquet CM, Knudson DL, Brown (1991)."Classification and nomenclature of viruses. Fifth Report of the International Committee on Taxonomy of Viruses"(PDF).Arch. Virol.: 107.Archived(PDF) from the original on 9 March 2023. Retrieved31 January 2023.
    3. Anshu A, Tan D, Chee SP, Mehta JS, Htoon HM (August 2017)."Interventions for the management of CMV-associated anterior segment inflammation".The Cochrane Database of Systematic Reviews.2017 (8): CD011908.doi:10.1002/14651858.cd011908.pub2.PMC 6483705.PMID 28838031.
    4. 4.04.14.2"Viral Zone". ExPASy.Archived from the original on 23 March 2017. Retrieved15 June 2015.
    5. 5.05.1"Virus Taxonomy: 2020 Release". International Committee on Taxonomy of Viruses (ICTV). March 2021.Archived from the original on 20 March 2020. Retrieved10 May 2021.
    6. 6.06.1Ryan KJ, Ray CG, eds. (2004).Sherris Medical Microbiology (4th ed.). McGraw Hill. pp. 556, 566–9.ISBN 978-0-8385-8529-0.
    7. Staeheli P, Haller O (December 2018)."Human MX2/MxB: a Potent Interferon-Induced Postentry Inhibitor of Herpesviruses and HIV-1".Journal of Virology.92 (24).doi:10.1128/JVI.00709-18.PMC 6258936.PMID 30258007.
    8. 8.08.18.2Koichi Y, Arvin AM, Campadelli-Fiume G, Mocarski E, Patrick M, Roizman B, Whitley R (2007).Human Herpesviruses: Biology, Therapy, and Immunoprophylaxis. Cambridge, UK: Cambridge University Press.ISBN 978-0-521-82714-0.
    9. "Panine betaherpesvirus 2 (Chimpanzee cytomegalovirus)".www.uniprot.org.Archived from the original on 24 January 2019. Retrieved13 March 2019.
    10. "Simian cytomegalovirus (strain Colburn)".www.uniprot.org.Archived from the original on 24 January 2019. Retrieved13 March 2019.
    11. "Macacine betaherpesvirus 3 (Rhesus cytomegalovirus)".www.uniprot.org.Archived from the original on 25 January 2019. Retrieved13 March 2019.
    12. "Murid herpesvirus 1, complete genome". 13 August 2018.Archived from the original on 23 April 2021. Retrieved13 March 2019 – via NCBI Nucleotide.
    13. 13.013.1Sijmons S, Van Ranst M, Maes P (March 2014)."Genomic and functional characteristics of human cytomegalovirus revealed by next-generation sequencing".Viruses.6 (3): 1049–1072.doi:10.3390/v6031049.PMC 3970138.PMID 24603756.
    14. Cannon MJ, Hyde TB, Schmid DS (July 2011)."Review of cytomegalovirus shedding in bodily fluids and relevance to congenital cytomegalovirus infection".Reviews in Medical Virology.21 (4): 240–255.doi:10.1002/rmv.695.PMC 4494736.PMID 21674676.
    15. Morgan K (3 April 2014)."Plasmids 101: The Promoter Region – Let's Go!".Addgene Blog.Archived from the original on 9 October 2015. Retrieved31 January 2023.
    16. Reddehase MJ, Lemmermann N, eds. (2006). "Preface".Cytomegaloviruses: Molecular Biology and Immunology. Horizon Scientific Press. pp. xxiv.ISBN 9781904455028.
    17. Craig JM, Macauley JC, Weller TH, Wirth P (January 1957). "Isolation of intranuclear inclusion producing agents from infants with illnesses resembling cytomegalic inclusion disease".Proceedings of the Society for Experimental Biology and Medicine.94 (1): 4–12.doi:10.3181/00379727-94-22841.PMID 13400856.S2CID 29263626.
    18. Chee MS, Bankier AT, Beck S, Bohni R, Brown CM, Cerny R, et al. (1990). "Analysis of the protein-coding content of the sequence of human cytomegalovirus strain AD169".Cytomegaloviruses. Current Topics in Microbiology and Immunology. Vol. 154. Springer Berlin Heidelberg. pp. 125–69.doi:10.1007/978-3-642-74980-3_6.ISBN 978-3-642-74982-7.PMID 2161319.
    19. Martí-Carreras J, Maes P (April 2019)."Human cytomegalovirus genomics and transcriptomics through the lens of next-generation sequencing: revision and future challenges".Virus Genes.55 (2): 138–164.doi:10.1007/s11262-018-1627-3.PMC 6458973.PMID 30604286.

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