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''Cytomegalovirus'' (CMV) (from ''cyto-'' 'cell' via
Greek Greek may refer to: 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 of all kno ...
- '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 spoken by the Latins (Italic tribe), Latins in Latium (now known as Lazio), the lower Tiber area aroun ...
'poison') is a genus of
virus A virus is a submicroscopic infectious agent that replicates only inside the living Cell (biology), cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea. Viruses are ...
es in the order ''
Herpesvirales ''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 cause ...
'', in the family ''
Herpesviridae ''Orthoherpesviridae'', previously named and more widely known as ''Herpesviridae'', is a large family of DNA viruses that cause infections and certain diseases in animals, including humans. The members of this family are commonly known as herp ...
'', 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 su ...
''.
Human Humans (''Homo sapiens'') or modern humans are the most common and widespread species of primate, and the last surviving species of the genus ''Homo''. They are Hominidae, great apes characterized by their Prehistory of nakedness and clothing ...
s and other
primate Primates is an order (biology), order of mammals, which is further divided into the Strepsirrhini, strepsirrhines, which include lemurs, galagos, and Lorisidae, lorisids; and the Haplorhini, haplorhines, which include Tarsiiformes, tarsiers a ...
s serve as natural
hosts A host is a person responsible for guests at an event or for providing hospitality during it. Host may also refer to: Places * Host, Pennsylvania, a village in Berks County * Host Island, in the Wilhelm Archipelago, Antarctica People * ...
. The 11 species in this genus include '' human betaherpesvirus 5'' (HCMV, human cytomegalovirus, HHV-5), which is the
species A species () is often defined as the largest group of organisms in which any two individuals of the appropriate sexes or mating types can produce fertile offspring, typically by sexual reproduction. It is the basic unit of Taxonomy (biology), ...
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 adu ...
and
pneumonia Pneumonia is an Inflammation, inflammatory condition of the lung primarily affecting the small air sacs known as Pulmonary alveolus, alveoli. Symptoms typically include some combination of Cough#Classification, productive or dry cough, ches ...
, and
congenital A birth defect is an abnormal condition that is present at childbirth, birth, regardless of its cause. Birth defects may result in disability, disabilities that may be physical disability, physical, intellectual disability, intellectual, or dev ...
CMV in infants can lead to deafness and ambulatory problems. 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 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 GTPases are a large family of hydrolase enzymes that bind to the nucleotide guanosine triphosphate (GTP) and hydrolyze it to guanosine diphosphate (GDP). The GTP binding and hydrolysis takes place in the highly conserved P-loop "G domain", a ...
activity.


Taxonomy

Within the ''
Herpesviridae ''Orthoherpesviridae'', previously named and more widely known as ''Herpesviridae'', is a large family of DNA viruses that cause infections and certain diseases in animals, including humans. The members of this family are commonly known as herp ...
'', 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 su ...
'' subfamily, which also includes the genera '' Muromegalovirus'' and '' Roseolovirus'' (
human herpesvirus 6 Human herpesvirus 6 (HHV-6) is the common collective name for human herpesvirus 6A (HHV-6A) and human herpesvirus 6B (HHV-6B). These closely related viruses are two of the nine known herpesviruses that have humans as their primary host. HHV-6 ...
and
human herpesvirus 7 Human herpesvirus 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'' (HHV ...
). 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) are two members of the Herpesviridae#Human herpesvirus types, human ''Herpesviridae'' family, a set of viruses that produce Viral disease, viral infections in the majority of humans. Both HSV-1 a ...
es 1 and 2 and varicella-zoster virus, 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), also known as human herpesvirus 4 (HHV-4), is one of the nine known Herpesviridae#Human herpesvirus types, human herpesvirus types in the Herpesviridae, herpes family, and is one of the most common viruses in ...
and
Kaposi's sarcoma-associated herpesvirus Kaposi's sarcoma-associated herpesvirus (KSHV) is the ninth known human herpesvirus. It is also called Human herpesvirus 8, or HHV-8 in short. This virus causes Kaposi's sarcoma, a cancer commonly occurring in AIDS patients, as well as primary ...
. Several species of ''Cytomegalovirus'' have been identified and classified for different
mammal A mammal () is a vertebrate animal of the Class (biology), class Mammalia (). Mammals are characterised by the presence of milk-producing mammary glands for feeding their young, a broad neocortex region of the brain, fur or hair, and three ...
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 simply known as the chimp, is a species of Hominidae, great ape native to the forests and savannahs of tropical Africa. It has four confirmed subspecies and a fifth proposed one. When its close rel ...
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 genus ...
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 Europe (in Gibraltar). Macaques are principally f ...
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''; 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
rat Rats are various medium-sized, long-tailed rodents. Species of rats are found throughout the order Rodentia, but stereotypical rats are found in the genus ''Rattus''. Other rat genera include '' Neotoma'' (pack rats), '' Bandicota'' (bandicoo ...
s.


Species

The following 11 species are assigned to the genus in ICTV 2022: * '' Cytomegalovirus aotinebeta1'' * '' Cytomegalovirus cebinebeta1'' * '' Cytomegalovirus cercopithecinebeta5'' * '' Cytomegalovirus humanbeta5'' * '' Cytomegalovirus macacinebeta3'' * '' Cytomegalovirus macacinebeta8'' * '' Cytomegalovirus mandrillinebeta1'' * '' Cytomegalovirus paninebeta2'' * '' Cytomegalovirus papiinebeta3'' * '' Cytomegalovirus papiinebeta4'' * '' Cytomegalovirus saimiriinebeta4''


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 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 genes, other functional regions of the genome such as ...
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 (sugar) 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 a ...
to host receptors, which mediates
endocytosis Endocytosis is a cellular process in which Chemical substance, 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 (biology and chem ...
. Replication follows the dsDNA bidirectional replication model. DNA templated transcription, with some
alternative splicing Alternative splicing, alternative RNA splicing, or differential splicing, is an alternative RNA splicing, splicing process during gene expression that allows a single gene to produce different splice variants. For example, some exons of a gene ma ...
mechanism is the method of transcription.
Translation Translation is the communication of the semantics, meaning of a #Source and target languages, source-language text by means of an Dynamic and formal equivalence, equivalent #Source and target languages, target-language text. The English la ...
takes place by leaky scanning. 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: Engineering * Latency (engineering), a measure of the time delay experienced by a system ** Latency (audio), the delay between the moment an audio signal is triggered and the moment it is produced or received ** Mec ...
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 many vertebrates including 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 min ...
s in humans and other
mammal A mammal () is a vertebrate animal of the Class (biology), class Mammalia (). Mammals are characterised by the presence of milk-producing mammary glands for feeding their young, a broad neocortex region of the brain, fur or hair, and three ...
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 Genetic engineering techniques, technologies used to change the genet ...
work conducted in
mammal A mammal () is a vertebrate animal of the Class (biology), class Mammalia (). Mammals are characterised by the presence of milk-producing mammary glands for feeding their young, a broad neocortex region of the brain, fur or hair, and three ...
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 *
Human cytomegalovirus Human cytomegalovirus (HCMV), also called human herpesvirus 5 (HHV-5), is a 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 call ...


References


External links


ICTV
{{Authority control Viral diseases Betaherpesvirinae Virus genera