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 indicating CMV infection of a lung pneumocyte{{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 = 612–4 | date = August 2000 | pmid = 11002765 | pmc = 1762915 | doi = 10.1136/jcp.53.8.612 }}

| taxon = Cytomegalovirus

| synonyms =

  • Human cytomegalovirus group

| synonyms_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 }}

| subdivision_ranks = Species

| subdivision = See text

}}

Cytomegalovirus (CMV) (from cyto- 'cell' via 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 viruses in the order Herpesvirales, in the family Herpesviridae,{{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 | pages = CD011908 | date = August 2017 | issue = 8 | pmid = 28838031 | pmc = 6483705 | doi = 10.1002/14651858.cd011908.pub2 }} in the subfamily Betaherpesvirinae. Humans and other primates serve as natural 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 mononucleosis and pneumonia,{{cite web|title=Viral Zone|url=http://viralzone.expasy.org/all_by_species/180.html|publisher=ExPASy|access-date=15 June 2015}}{{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}} and congenital CMV in infants can lead to deafness and ambulatory problems.{{cite web|title=Often overlooked, a common infection during pregnancy kickstarts a conversation about newborn screening|date=5 April 2023 |url=https://www.statnews.com/2023/04/05/cmv-screening-congenital-cytomegalovirus-hearing-loss|publisher=STAT|access-date=5 April 2023}}

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.{{cite book | veditors = Ryan KJ, Ray CG | title = Sherris Medical Microbiology | edition = 4th | pages = 556; 566–9 | publisher = McGraw Hill | year = 2004 | isbn = 978-0-8385-8529-0 }}

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.{{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 }}

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).{{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 }} It is also related to other herpesviruses within the Alphaherpesvirinae subfamily, which includes herpes simplex viruses 1 and 2 and varicella-zoster virus, and the Gammaherpesvirinae subfamily, which includes Epstein–Barr virus and Kaposi's sarcoma-associated herpesvirus.

Several species of Cytomegalovirus have been identified and classified for different mammals. 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 chimpanzees and orangutans, and Simian cytomegalovirus (SCCMV) and Rhesus cytomegalovirus (RhCMV) that infect macaques; CCMV is known as both Panine beta herpesvirus 2 (PaHV-2) and Pongine betaherpesvirus 4 (PoHV-4).{{cite web|url=https://www.uniprot.org/taxonomy/188763|title=Panine betaherpesvirus 2 (Chimpanzee cytomegalovirus)|website=www.uniprot.org|access-date=13 March 2019}} SCCMV is called cercopithecine betaherpesvirus 5 (CeHV-5){{cite web|url=https://www.uniprot.org/taxonomy/50292|title=Simian cytomegalovirus (strain Colburn)|website=www.uniprot.org|access-date=13 March 2019}} and RhCMV, Cercopithecine betaherpesvirus 8 (CeHV-8).{{cite web|url=https://www.uniprot.org/taxonomy/47929|title=Macacine betaherpesvirus 3 (Rhesus cytomegalovirus)|website=www.uniprot.org|access-date=13 March 2019}} 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 rats.{{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}}

= Species =

Structure

File:CMVschema.svg

Viruses in Cytomegalovirus 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.

class="wikitable sortable" style="text-align:center"
GenusStructure || SymmetryCapsidGenomic arrangementGenomic segmentation
CytomegalovirusSpherical pleomorphicT=16EnvelopedLinearMonopartite

Genome

File:HCMV genome.png

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".{{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 }}

{{anchor|Lifecycle}}Life cycle

Viral replication is nuclear and lysogenic. Entry into the host cell is achieved by attachment of the viral glycoproteins to host receptors, which mediates endocytosis. Replication follows the dsDNA bidirectional replication model. DNA templated transcription, with some alternative splicing mechanism is the method of transcription. Translation takes place by leaky scanning. The virus exits the host cell by [http://viralzone.expasy.org/all_by_species/1952.html nuclear egress], and 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.{{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 }}

class="wikitable sortable" style="text-align:center"
GenusHost detailsTissue tropismEntry detailsRelease detailsReplication siteAssembly siteTransmission
Cytomegalovirushumans; monkeysEpithelial mucosaGlycoproteinsBuddingNucleusNucleusUrine; saliva; congenital

All herpesviruses share a characteristic ability to remain latent within the body over long periods. Although they may be found throughout the body, CMV infections are frequently associated with the salivary glands in humans and other mammals.

Genetic engineering

The CMV promoter is commonly included in vectors used in genetic engineering work conducted in mammalian cells, as it is a strong promoter and drives constitutive expression of genes under its control.{{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! }}

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.{{Cite book | veditors = Reddehase MJ, Lemmermann N | pages = xxiv |chapter=Preface |title=Cytomegaloviruses: Molecular Biology and Immunology |publisher=Horizon Scientific Press |year=2006 |isbn=9781904455028 }} Years later, between 1956 and 1957, Thomas Huckle Weller together with Smith and Rowe independently isolated the virus, known thereafter as "cytomegalovirus".{{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 }} In 1990, the first draft of human cytomegalovirus genome was published,{{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 = 125–69 | 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 }} the biggest contiguous genome sequenced at that time.{{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 }}

See also

References

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