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.
|Typical "owl eye" intranuclear inclusion indicating CMV infection of a lung pneumocyte|
|Human betaherpesvirus 5|
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:
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 contact, urine, and saliva.
|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.
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