''Cytomegalovirus'' (CMV) (from ''cyto-'' 'cell' via
Greek - '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'', in the family ''
Herpesviridae'', in the subfamily ''
Betaherpesvirinae''.
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. 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 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, 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'', CMV belongs to the ''
Betaherpesvirinae'' subfamily, which also includes the genera ''
Muromegalovirus'' and ''
Roseolovirus'' (
human herpesvirus 6 and
human herpesvirus 7).
It is also related to other herpesviruses within the ''
Alphaherpesvirinae'' 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'' subfamily, which includes
Epstein–Barr virus and
Kaposi's sarcoma-associated herpesvirus.
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
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.
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 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
References
External links
ICTV
{{Authority control
Viral diseases
Betaherpesvirinae
Virus genera