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''Cytomegalovirus'' (''CMV'') (from ''cyto-'' 'cell' via
Greek Greek may refer to: Greece Anything of, from, or related to Greece, a country in Southern Europe: *Greeks, an ethnic group. *Greek language, a branch of the Indo-European language family. **Proto-Greek language, the assumed last common ancestor ...
- 'container' + 'big, megalo-' + -''virus'' via
Latin Latin (, or , ) is a classical language belonging to the Italic languages, Italic branch of the Indo-European languages. Latin was originally a dialect spoken in the lower Tiber area (then known as Latium) around present-day Rome, but through ...
'poison') is a genus of
virus A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea. Since Dmitri Ivanovsk ...
es in the order ''
Herpesvirales The ''Herpesvirales'' is an order of dsDNA viruses (Baltimore group I) with animal hosts, characterised by a common morphology consisting of an icosahedral capsid enclosed in a glycoprotein-containing lipid envelope. Common infections in humans ...
'', in the family ''
Herpesviridae ''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 ''ἕρπει� ...
'', in the subfamily ''
Betaherpesvirinae ''Betaherpesvirinae'' is a subfamily of viruses in the order ''Herpesvirales'' and in the family ''Herpesviridae''. Mammals serve as natural hosts. There are 26 species in this subfamily, divided among 5 genera. Diseases associated with this sub ...
''. Humans and other primates serve as natural hosts. The 11 species in this genus include ''
human betaherpesvirus 5 ''Human betaherpesvirus 5'', also called human cytomegalovirus (HCMV), is species of virus in the genus ''Cytomegalovirus'', which in turn is a member of the viral family known as ''Herpesviridae'' or herpesviruses. It is also commonly called ...
'' (HCMV, human cytomegalovirus, HHV-5), which is the
species In biology, a species is the basic unit of classification and a taxonomic rank of an organism, as well as a unit of biodiversity. A species is often defined as the largest group of organisms in which any two individuals of the appropriat ...
that infects humans. Diseases associated with HHV-5 include
mononucleosis Infectious mononucleosis (IM, mono), also known as glandular fever, is an infection usually caused by the Epstein–Barr virus (EBV). Most people are infected by the virus as children, when the disease produces few or no symptoms. In young adult ...
and
pneumonia Pneumonia is an inflammatory condition of the lung primarily affecting the small air sacs known as alveoli. Symptoms typically include some combination of productive or dry cough, chest pain, fever, and difficulty breathing. The severit ...
. In the
medical literature Medical literature is the scientific literature of medicine: articles in journals and texts in books devoted to the field of medicine. Many references to the medical literature include the health care literature generally, including that of denti ...
, most mentions of CMV without further specification refer implicitly to human CMV. Human CMV is the most studied of all cytomegaloviruses. 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.


Taxonomy

Within the ''
Herpesviridae ''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 ''ἕρπει� ...
'', CMV belongs to the ''
Betaherpesvirinae ''Betaherpesvirinae'' is a subfamily of viruses in the order ''Herpesvirales'' and in the family ''Herpesviridae''. Mammals serve as natural hosts. There are 26 species in this subfamily, divided among 5 genera. Diseases associated with this sub ...
'' subfamily, which also includes the genera ''
Muromegalovirus ''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 three species in this genus. Diseases associated with ...
'' and ''
Roseolovirus ''Roseolovirus'' is a genus of viruses in the order ''Herpesvirales'', in the family ''Herpesviridae'', in the subfamily ''Betaherpesvirinae''. There are currently six species in this genus. Diseases associated with this genus include: HHV-6: si ...
'' (
human herpesvirus 6 Human herpesvirus 6 (HHV-6) is the common collective name for '' human betaherpesvirus 6A'' (HHV-6A) and '' human betaherpesvirus 6B'' (HHV-6B). These closely related viruses are two of the nine known herpesviruses that have humans as their prim ...
and ''
human betaherpesvirus 7 ''Human betaherpesvirus 7'' (HHV-7) is one of nine known members of the ''Herpesviridae'' family that infects humans. HHV-7 is a member of ''Betaherpesvirinae'', a subfamily of the ''Herpesviridae'' that also includes HHV-6 and ''Cytomegalovirus ...
''). It is also related to other herpesviruses within the ''
Alphaherpesvirinae ''Alphaherpesvirinae'' is a subfamily of viruses in the family ''Herpesviridae'', primarily distinguished by reproducing more quickly than other subfamilies in the ''Herpesviridae''. In animal virology the most important herpesviruses belong to ...
'' subfamily, which includes
herpes simplex virus Herpes simplex virus 1 and 2 (HSV-1 and HSV-2), also known by their taxonomical names '' Human alphaherpesvirus 1'' and ''Human alphaherpesvirus 2'', are two members of the human ''Herpesviridae'' family, a set of viruses that produce viral in ...
es 1 and 2 and
varicella-zoster virus Varicella-zoster virus (VZV), also known as human herpesvirus 3 (HHV-3, HHV3) or ''Human alphaherpesvirus 3'' (taxonomically), is one of nine known herpes viruses that can infect humans. It causes chickenpox (varicella) commonly affecting chil ...
, and the ''
Gammaherpesvirinae ''Gammaherpesvirinae'' is a subfamily of viruses in the order ''Herpesvirales'' and in the family ''Herpesviridae''. Viruses in ''Gammaherpesvirinae'' are distinguished by reproducing at a more variable rate than other subfamilies of ''Herpesvir ...
'' subfamily, which includes
Epstein–Barr virus The Epstein–Barr virus (EBV), formally called ''Human gammaherpesvirus 4'', is one of the nine known human herpesvirus types in the herpes family, and is one of the most common viruses in humans. EBV is a double-stranded DNA virus. It is ...
and
Kaposi's sarcoma-associated herpesvirus Kaposi's sarcoma-associated herpesvirus (KSHV) is the ninth known human herpesvirus; its formal name according to the International Committee on Taxonomy of Viruses (ICTV) is ''Human gammaherpesvirus 8'', or HHV-8 in short. Like other herpesvir ...
. Several species of ''Cytomegalovirus'' have been identified and classified for different
mammal Mammals () are a group of vertebrate animals constituting the class Mammalia (), characterized by the presence of mammary glands which in females produce milk for feeding (nursing) their young, a neocortex (a region of the brain), fur ...
s. 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
chimpanzee The chimpanzee (''Pan troglodytes''), also known as simply the chimp, is a species of great ape native to the forest and savannah of tropical Africa. It has four confirmed subspecies and a fifth proposed subspecies. When its close relative t ...
s and
orangutan Orangutans are great apes native to the rainforests of Indonesia and Malaysia. They are now found only in parts of Borneo and Sumatra, but during the Pleistocene they ranged throughout Southeast Asia and South China. Classified in the genu ...
s, and ''Simian cytomegalovirus'' (SCCMV) and ''Rhesus cytomegalovirus'' (RhCMV) that infect
macaque The macaques () constitute a genus (''Macaca'') of gregarious Old World monkeys of the subfamily Cercopithecinae. The 23 species of macaques inhabit ranges throughout Asia, North Africa, and (in one instance) Gibraltar. Macaques are principall ...
s; 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 Night monkeys, also known as owl monkeys or douroucoulis (), are nocturnal New World monkeys of the genus ''Aotus'', the only member of the family Aotidae (). The genus comprises eleven species which are found across Panama and much of South Am ...
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 ''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 three species in this genus. Diseases associated with ...
''; 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.


Species

The genus consists of these 11 species: * ''
Aotine betaherpesvirus 1 ''Aotine betaherpesvirus 1'' (AoHV-1) is a species of virus in the genus '' Cytomegalovirus'', subfamily ''Betaherpesvirinae'', family ''Herpesviridae'', and order ''Herpesvirales''. Night monkey Night monkeys, also known as owl monkeys or d ...
'' * ''
Cebine betaherpesvirus 1 ''Cebine betaherpesvirus 1'' (CbHV-1) is a species of virus in the genus '' Cytomegalovirus'', subfamily ''Betaherpesvirinae'', family ''Herpesviridae'', and order ''Herpesvirales The ''Herpesvirales'' is an order of dsDNA viruses (Baltimore g ...
'' * ''
Cercopithecine betaherpesvirus 5 ''Cercopithecine betaherpesvirus 5'' (CeHV-5) is a species of virus in the genus '' Cytomegalovirus'', subfamily ''Betaherpesvirinae'', family ''Herpesviridae'', and order ''Herpesvirales''. African green monkey ''Chlorocebus'' is a genus of ...
'' * ''
Human betaherpesvirus 5 ''Human betaherpesvirus 5'', also called human cytomegalovirus (HCMV), is species of virus in the genus ''Cytomegalovirus'', which in turn is a member of the viral family known as ''Herpesviridae'' or herpesviruses. It is also commonly called ...
'' * '' Macacine betaherpesvirus 3'' * '' Macacine betaherpesvirus 8'' * '' Mandrilline betaherpesvirus 1'' * '' Panine betaherpesvirus 2'' * ''
Papiine betaherpesvirus 3 ''Papiine betaherpesvirus 3'' (PaHV-3) is a species of virus in the genus ''Cytomegalovirus'', subfamily ''Betaherpesvirinae'', family ''Herpesviridae'', and order ''Herpesvirales The ''Herpesvirales'' is an order of dsDNA viruses (Baltimore g ...
'' * ''
Papiine betaherpesvirus 4 ''Papiine betaherpesvirus 4'' (PaHV-4) is a species of virus in the genus ''Cytomegalovirus'', subfamily ''Betaherpesvirinae'', family ''Herpesviridae'', and order ''Herpesvirales The ''Herpesvirales'' is an order of dsDNA viruses (Baltimore g ...
'' * '' Saimiriine betaherpesvirus 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.


Genome

Herpesviruses have some of the largest genomes among human viruses, often encoding hundreds of proteins. For instance, the double‑stranded DNA (dsDNA)
genome In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding ...
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".


Life cycle

Viral replication is nuclear and lysogenic. Entry into the host cell is achieved by attachment of the viral
glycoproteins Glycoproteins are proteins which contain oligosaccharide chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycosy ...
to host receptors, which mediates
endocytosis Endocytosis is a cellular process in which substances are brought into the cell. The material to be internalized is surrounded by an area of cell membrane, which then buds off inside the cell to form a vesicle containing the ingested material. ...
. Replication follows the dsDNA bidirectional replication model. DNA templated transcription, with some
alternative splicing Alternative splicing, or alternative RNA splicing, or differential splicing, is an alternative splicing process during gene expression that allows a single gene to code for multiple proteins. In this process, particular exons of a gene may be i ...
mechanism is the method of transcription.
Translation Translation is the communication of the meaning of a source-language text by means of an equivalent target-language text. The English language draws a terminological distinction (which does not exist in every language) between ''transla ...
takes place by
leaky scanning Leaky scanning is a mechanism used during the initiation phase of eukaryotic translation that enables regulation of gene expression. During initiation, the small 40S ribosomal subunit (as a 43S PIC) "scans" or moves in a 5' --> 3' direction along ...
. The virus exits the host cell b
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. All herpesviruses share a characteristic ability to remain
latent Latency or latent may refer to: Science and technology * Latent heat, energy released or absorbed, by a body or a thermodynamic system, during a constant-temperature process * Latent variable, a variable that is not directly observed but inferred ...
within the body over long periods. Although they may be found throughout the body, CMV infections are frequently associated with the
salivary gland The salivary glands in mammals are exocrine glands that produce saliva through a system of ducts. Humans have three paired major salivary glands ( parotid, submandibular, and sublingual), as well as hundreds of minor salivary glands. Salivary ...
s in humans and other
mammal Mammals () are a group of vertebrate animals constituting the class Mammalia (), characterized by the presence of mammary glands which in females produce milk for feeding (nursing) their young, a neocortex (a region of the brain), fur ...
s.


Genetic engineering

The CMV promoter is commonly included in vectors used in
genetic engineering Genetic engineering, also called genetic modification or genetic manipulation, is the modification and manipulation of an organism's genes using technology. It is a set of technologies used to change the genetic makeup of cells, including ...
work conducted in
mammal Mammals () are a group of vertebrate animals constituting the class Mammalia (), characterized by the presence of mammary glands which in females produce milk for feeding (nursing) their young, a neocortex (a region of the brain), fur ...
ian cells, as it is a strong promoter and drives constitutive expression of genes under its control.


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. 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.


See also

*
CMV polyradiculomyelopathy CMV polyradiculomyelopathy (PRAM) is one of the five distinct neurological syndromes caused by CMV in HIV/AIDS. It causes subacute ascending lower extremity weakness with paresthesias and radicular pain, hyporeflexia or areflexia, and urinary r ...
*
Human cytomegalovirus ''Human betaherpesvirus 5'', also called human cytomegalovirus (HCMV), is species of virus in the genus '' Cytomegalovirus'', which in turn is a member of the viral family known as '' Herpesviridae'' or herpesviruses. It is also commonly cal ...


References


External links


ICTV
{{Use dmy dates, date=April 2017 Viral diseases Betaherpesvirinae Virus genera