From Wikipedia the free encyclopedia
|Typical "owl eye" intranuclear inclusion indicating CMV infection of a lung pneumocyte|
|Human betaherpesvirus 5|
Cytomegalovirus (CMV) (from the Greek cyto-, "cell," and megalo-, "large") is a genus of viruses in the order Herpesvirales, in the family Herpesviridae, in the subfamily Betaherpesvirinae. Humans and monkeys serve as natural hosts. The eight species in this genus include the type species, human betaherpesvirus 5 (HCMV, human cytomegalovirus, HHV-5), which is the species that infects humans. Diseases associated with HHV-5 include mononucleosis, and pneumonia. 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.
Within the Herpesviridae, CMV belongs to the Betaherpesvirinae subfamily, which also includes the genera Muromegalovirus and Roseolovirus (human herpesvirus 6 and human betaherpesvirus 7). 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). SCCMV is called cercopithecine betaherpesvirus 5 (CeHV-5) and RhCMV, Cercopithecine betaherpesvirus 8 (CeHV-8). 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.
The genus consists of these 11 species:
- Aotine betaherpesvirus 1
- Cebine betaherpesvirus 1
- Cercopithecine betaherpesvirus 5
- Human betaherpesvirus 5
- Macacine betaherpesvirus 3
- Macacine betaherpesvirus 8
- Mandrilline betaherpesvirus 1
- Panine betaherpesvirus 2
- Papiine betaherpesvirus 3
- Papiine betaherpesvirus 4
- Saimiriine betaherpesvirus 4
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.
|Genus||Structure||Symmetry||Capsid||Genomic arrangement||Genomic segmentation|
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”.
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 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.
|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|
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.
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.
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. Years later, between 1956 and 1957, Thomas Huckle Weller together with Smith and Rowe independently isolated the virus, known thereafter as “cytomegalovirus”. In 1990, the first draft of human cytomegalovirus genome was published, the biggest contiguous genome sequenced at that time.
In January 2020, scientists at Rockefeller University led by Jean-Laurent Casanova discovered that there may be a link between a deficiency in nitric oxide synthase 2 (NOS2) and fatal cases of CMV. This finding may lead to new treatments for patients with CMV and new genetic screening approaches to discover those who are vulnerable to the virus due to a deficiency in NOS2.
- 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.
- Francki RI, Fauquet CM, Knudson DL, Brown (1991). "Classification and nomenclature of viruses. Fifth Report of the International Committee on Texonomy of Viruses" (PDF). Arch. Virol.: 107.
- 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. 8: CD011908. doi:10.1002/14651858.cd011908.pub2. PMC 6483705. PMID 28838031.
- "Viral Zone". ExPASy. Retrieved 15 June 2015.
- ICTV. "Virus Taxonomy: 2014 Release". Retrieved 15 June 2015.
- Ryan KJ, Ray CG, eds. (2004). Sherris Medical Microbiology (4th ed.). McGraw Hill. pp. 556, 566–9. ISBN 978-0-8385-8529-0.
- Yamanishi K, Arvin AM, Campadelli-Fiume G, Mocarski E, Moore P, Roizman B, Whitley R (2007). Human Herpesviruses: Biology, Therapy, and Immunoprophylaxis. Cambridge, UK: Cambridge University Press. ISBN 978-0-521-82714-0.
- "Panine betaherpesvirus 2 (Chimpanzee cytomegalovirus)". www.uniprot.org. Retrieved 13 March 2019.
- "Simian cytomegalovirus (strain Colburn)". www.uniprot.org. Retrieved 13 March 2019.
- "Macacine betaherpesvirus 3 (Rhesus cytomegalovirus)". www.uniprot.org. Retrieved 13 March 2019.
- "Murid herpesvirus 1, complete genome". 13 August 2018. Retrieved 13 March 2019 – via NCBI Nucleotide.
- Sijmons, Steven; Van Ranst, Marc; Maes, Piet (5 March 2014). "Genomic and functional characteristics of human cytomegalovirus revealed by next-generation sequencing". Viruses. 6 (3): 1049–1072. doi:10.3390/v6031049. ISSN 1999-4915. PMC 3970138. PMID 24603756.
- Cannon, Michael J.; Hyde, Terri B.; Schmid, D. Scott (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. ISSN 1052-9276. PMC 4494736. PMID 21674676.
- Morgan K (3 April 2014). "Plasmids 101: The Promoter Region – Let's Go!". Addgene Blog.
- Reddehase MJ, Lemmermann N, eds. (2006). "Preface". Cytomegaloviruses: Molecular Biology and Immunology. Horizon Scientific Press. pp. xxiv. ISBN 9781904455028.
- 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.
- 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. 154. Springer Berlin Heidelberg. pp. 125–69. doi:10.1007/978-3-642-74980-3_6. ISBN 978-3-642-74982-7. PMID 2161319.
- 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.
- Casanova, Jean-Laurent (29 January 2020). "Patient with unusually severe infection leads scientists to a rare type of immune deficiency". Rockefeller University. Retrieved 14 March 2020.
|Wikimedia Commons has media related to Cytomegalovirus.|
|Wikispecies has information related to Cytomegalovirus.|