Cytomegalovirus

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Cytomegalovirus
Cytomegalovirus 01.jpg
Typical "owl eye" inclusion indicating CMV infection of a lung pneumocyte [1]
Virus classification Red Pencil Icon.png
(unranked): Virus
Phylum: incertae sedis
Class: incertae sedis
Order: Herpesvirales
Family: Herpesviridae
Subfamily: Betaherpesvirinae
Genus:Cytomegalovirus
Type species
Human betaherpesvirus 5
Species

See text

Synonyms [2]
  • Human cytomegalovirus group

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. [3] [4] 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. [5]

Contents

Taxonomy

Within the Herpesviridae , CMV belongs to the Betaherpesvirinae subfamily, which also includes the genera Muromegalovirus and Roseolovirus (human herpesvirus 6 and Human betaherpesvirus 7 ). [6] 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. [5]

Several species of Cytomegalovirus have been identified and classified for different mammals. [6] 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). [7] SCCMV is called cercopithecine betaherpesvirus 5 (CeHV-5) [8] and RhCMV, Cercopithecine betaherpesvirus 8 (CeHV-8). [9] 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. [10]

Species

The genus consists of these 11 species: [4]

Structure

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. [3]

GenusStructureSymmetryCapsidGenomic arrangementGenomic segmentation
CytomegalovirusSpherical pleomorphicT=16EnvelopedLinearMonopartite

Lifecycle

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 contact, urine, and saliva. [3]

GenusHost detailsTissue tropismEntry detailsRelease detailsReplication siteAssembly siteTransmission
CytomegalovirusHumans; monkeysEpithelial mucosaGlycoproteinsBuddingNucleusNucleusUrine; 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. [6]

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. [11]

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. [12] Years later, between 1956 and 1957, Thomas Huckle Weller together with Smith and Rowe independently isolated the virus, known thereafter as “cytomegalovirus”. [13] In 1990, the first draft of human cytomegalovirus genome was published [14] , the biggest contiguous genome sequenced at that time. [15]

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. [16]

See also

Related Research Articles

Roseolovirus is a genus of viruses in the order Herpesvirales, in the family Herpesviridae, in the subfamily Betaherpesvirinae. Humans serve as natural hosts. There are currently three species in this genus including the type species Human betaherpesvirus 6A. Diseases associated with this genus include: HHV-6: sixth disease ; HHV-7: symptoms analog to the 'sixth disease'.

Rhadinovirus is a genus of viruses in the order Herpesvirales, in the family Herpesviridae, in the subfamily Gammaherpesvirinae. Humans and other mammals serve as natural hosts. There are currently nine species in this genus including the type species Saimiriine gammaherpesvirus 2. Diseases associated with this genus include: Kaposi's sarcoma, primary effusion lymphoma and multicentric Castleman's disease, caused by Human gammaherpesvirus 8 (HHV-8), also known as Kaposi's sarcoma-associated herpesvirus (KSHV). The term rhadino comes from the Latin fragile, referring to the tendency of the viral genome to break apart when it is isolated.

<i>Herpesviridae</i> family of viruses

Herpesviridae is a large family of DNA viruses that cause infections and certain diseases in animals, including humans. The members of this family are also known as herpesviruses. The family name is derived from the Greek word herpein, referring to spreading cutaneous lesions, usually involving blisters, seen in flares of herpes simplex 1, herpes simplex 2 and herpes zoster (shingles). In 1971, the International Committee on the Taxonomy of Viruses (ICTV) established Herpesvirus as a genus with 23 viruses among four groups. Latent, recurring infections are typical of this group of viruses, though the family name does not refer to latency. Herpesviridae can cause latent or lytic infections.

Betaherpesvirinae is a subfamily of viruses in the order Herpesvirales and in the family Herpesviridae. Mammals serve as natural hosts. There are currently 18 species in this subfamily, divided among 4 genera. Diseases associated with this subfamily include: human cytomegalovirus (HHV-5): congenital CMV infection; HHV-6: 'sixth disease' ; HHV-7: symptoms analogous to the 'sixth disease'.

Macacine alphaherpesvirus 1, Herpesvirus simiae, or Herpes virus B) is the Simplexvirus infecting macaque monkeys. Macacine alphaherpesvirus 1 is an alphaherpesvirus, which consists of a subset of herpes viruses that travel within hosts using the peripheral nerves. As such, this neurotropic virus is not found in the blood.

<i>Lymphocryptovirus</i> Genus of viruses

Lymphocryptovirus is a genus of viruses in the order Herpesvirales, in the family Herpesviridae, in the subfamily Gammaherpesvirinae. This genus includes the human-infecting Human gammaherpesvirus 4, as well as viruses that infect both Old World monkeys and New World monkeys. Other names for the Lymphocryptovirus genus include Lymphocryptoviridae and gamma-1 herpesviruses. There are currently eight species in this genus including the type species Human gammaherpesvirus 4. Diseases associated with this genus include: mononucleosis, Burkitt's lymphoma, and nasopharyngeal carcinoma.

<i>Simplexvirus</i> genus of viruses

Simplexvirus is a genus of viruses in the order Herpesvirales, in the family Herpesviridae, in the subfamily Alphaherpesvirinae. Humans and mammals serve as natural hosts. Diseases associated with this genus include skin vesicles or mucosal ulcers, rarely encephalitis, and meningitis.

<i>Herpesvirales</i> order of viruses

The Herpesvirales is an order of dsDNA viruses with animal hosts, characterised by a common morphology consisting of an icosahedral capsid enclosed in a glycoprotein-containing lipid envelope. Common infections in humans caused by members of this order include cold sores, genital herpes, chickenpox, shingles, and glandular fever.

Muromegalovirus is a genus of viruses in the order Herpesvirales, in the family Herpesviridae, in the subfamily Betaherpesvirinae. Rodents serve as natural hosts. There are currently three species in this genus including the type species Murid betaherpesvirus 1. Diseases associated with this genus include: infected peritoneal macrophages, dendritic cells (DC) and hepatocytes, inducing significant pathology in both the spleen and the liver. Murid viruses Murid betaherpesvirus 1 (MuHV-1) and Murid betaherpesvirus 2 (MuHV-2), previously defined as mouse cytomegalovirus (MCMV) and rat cytomegalovirus (RCMV), belong to this genus.

Cercopithecine betaherpesvirus 5 (CeHV-5) is a species of virus in the genus Cytomegalovirus, subfamily Betaherpesvirinae, family Herpesviridae, and order Herpesvirales.

Macacine betaherpesvirus 3 (McHV-3) is a species of virus in the genus Cytomegalovirus, subfamily Betaherpesvirinae, family Herpesviridae, and order Herpesvirales.

Panine betaherpesvirus 2 (PnHV-2) is a species of virus in the genus Cytomegalovirus, subfamily Betaherpesvirinae, family Herpesviridae, and order Herpesvirales.

Papiine betaherpesvirus 3 (PaHV-3) is a species of virus in the genus Cytomegalovirus, subfamily Betaherpesvirinae, family Herpesviridae, and order Herpesvirales.

Papiine betaherpesvirus 4 (PaHV-4) is a species of virus in the genus Cytomegalovirus, subfamily Betaherpesvirinae, family Herpesviridae, and order Herpesvirales.

Saimiriine betaherpesvirus 4 (SaHV-4) is a species of virus in the genus Cytomegalovirus, subfamily Betaherpesvirinae, family Herpesviridae, and order Herpesvirales.

Murid betaherpesvirus 1 (MuHV-1) is a species of virus in the genus Muromegalovirus, subfamily Betaherpesvirinae, family Herpesviridae, and order Herpesvirales.

Murid betaherpesvirus 2 (MuHV-2) is a species of virus in the genus Muromegalovirus, subfamily Betaherpesvirinae, family Herpesviridae, and order Herpesvirales.

Murid betaherpesvirus 8 (MuHV-8) is a species of virus in the genus Muromegalovirus, subfamily Betaherpesvirinae, family Herpesviridae, and order Herpesvirales.

<i>Human betaherpesvirus 6B</i> species of virus

Human betaherpesvirus 6B (HHV-6B) is a species of virus in the genus Roseolovirus, subfamily Betaherpesvirinae, family Herpesviridae, and order Herpesvirales.

Macacine betaherpesvirus 9 (McHV-9) is a species of virus in the genus Roseolovirus, subfamily Betaherpesvirinae, family Herpesviridae, and order Herpesvirales.

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". J. Clin. Pathol. 53 (8): 612–4. doi:10.1136/jcp.53.8.612. PMC   1762915 . PMID   11002765.
  2. Francki, R. I. B., Fauquet, C. M., Knudson, D. L. & Brown, F. (eds)(1991). Classification and nomenclature of viruses. Fifthreport of the International Committee on Taxonomy of Viruses. Archives of Virology Supplementum 2, p.107 https://talk.ictvonline.org/ictv/proposals/ICTV%205th%20Report.pdf
  3. 1 2 3 "Viral Zone". ExPASy. Retrieved 15 June 2015.
  4. 1 2 ICTV. "Virus Taxonomy: 2014 Release" . Retrieved 15 June 2015.
  5. 1 2 Ryan KJ, Ray CG, eds. (2004). Sherris Medical Microbiology (4th ed.). McGraw Hill. pp. 556, 566–9. ISBN   978-0-8385-8529-0.
  6. 1 2 3 Koichi Yamanishi; Arvin, Ann M; Gabriella Campadelli-Fiume; Edward Mocarski; Moore, Patrick; Roizman, Bernard; Whitley, Richard (2007). Human Herpesviruses: Biology, Therapy, and Immunoprophylaxis. Cambridge, UK: Cambridge University Press. ISBN   978-0-521-82714-0.
  7. "Panine betaherpesvirus 2 (Chimpanzee cytomegalovirus)". www.uniprot.org. Retrieved 13 March 2019.
  8. "Simian cytomegalovirus (strain Colburn)". www.uniprot.org. Retrieved 13 March 2019.
  9. "Macacine betaherpesvirus 3 (Rhesus cytomegalovirus)". www.uniprot.org. Retrieved 13 March 2019.
  10. "Murid herpesvirus 1, complete genome". 13 August 2018. Retrieved 13 March 2019 via NCBI Nucleotide.Cite journal requires |journal= (help)
  11. Kendall Morgan for Addgene Blog. Apr 3, 2014 Plasmids 101: The Promoter Region – Let's Go!
  12. Reddehase, Matthias J.; Lemmermann, Niels, eds. (2006). "Preface". Cytomegaloviruses: Molecular Biology and Immunology. Horizon Scientific Press. pp. xxiv. ISBN   9781904455028.
  13. Weller, T. H.; MacAuley, J. C.; Craig, J. M.; Wirth, P. (1 January 1957). "Isolation of Intranuclear Inclusion Producing Agents from Infants with Illnesses Resembling Cytomegalic Inclusion Disease". Experimental Biology and Medicine. 94 (1): 4–12. doi:10.3181/00379727-94-22841. PMID   13400856.
  14. Chee, M. S.; Bankier, A. T.; Beck, S.; Bohni, R.; Brown, C. M.; Cerny, R.; Horsnell, T.; Hutchison, C. A.; Kouzarides, T.; Martignetti, J. A.; Preddie, E.; Satchwell, S. C.; Tomlinson, P.; Weston, K. M.; Barrell, B. G. (1990). "Analysis of the Protein-Coding Content of the Sequence of Human Cytomegalovirus Strain AD169". Cytomegaloviruses. Current Topics in Microbiology and Immunology. Springer Berlin Heidelberg. 154: 125–169. doi:10.1007/978-3-642-74980-3_6. ISBN   978-3-642-74982-7. PMID   2161319.
  15. Martí-Carreras, Joan; Maes, Piet (2 January 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.
  16. "Patient with unusually severe infection leads scientists to a rare type of immune deficiency". News. Retrieved 5 February 2020.
Classification
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External resources