Cytomegalovirus Infections
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''Cytomegalovirus'' (''CMV'') (from ''cyto-'' 'cell' via Greek - 'container' + 'big, megalo-' + -''virus'' via Latin 'poison') is a genus of viruses in the order '' Herpesvirales'', in the family '' Herpesviridae'', in the subfamily '' Betaherpesvirinae''. Humans and other primates serve as natural hosts. The 11 species in this genus include '' 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. 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'', 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 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 inf ...
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 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 or ...
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 th ...
s and orangutans, 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 principally ...
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 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'' (bandicoot ...
s.


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'' * ''
Macacine betaherpesvirus 3 ''Macacine betaherpesvirus 3'' (McHV-3) is a species of virus in the genus ''Cytomegalovirus ''Cytomegalovirus'' (''CMV'') (from ''cyto-'' 'cell' via Greek - 'container' + 'big, megalo-' + -''virus'' via Latin 'poison') is a genus of virus ...
'' * ''
Macacine betaherpesvirus 8 ''Macacine betaherpesvirus 8'' (McHV-8) 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 ...
'' * ''
Mandrilline betaherpesvirus 1 ''Mandrilline betaherpesvirus 1'' (MleuCMV) is a species of virus 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 fam ...
'' * ''
Panine betaherpesvirus 2 ''Panine betaherpesvirus 2'' (PnHV-2) is a species of virus in the genus ''Cytomegalovirus ''Cytomegalovirus'' (''CMV'') (from ''cyto-'' 'cell' via Greek - 'container' + 'big, megalo-' + -''virus'' via Latin 'poison') is a genus of viruses ...
'' * ''
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 ''Saimiriine betaherpesvirus 4'' (SaHV-4) is a species of virus in the genus ''Cytomegalovirus ''Cytomegalovirus'' (''CMV'') (from ''cyto-'' 'cell' via Greek - 'container' + 'big, megalo-' + -''virus'' via Latin 'poison') is a genus of vir ...
''


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 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 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. E ...
.
Replication Replication may refer to: Science * Replication (scientific method), one of the main principles of the scientific method, a.k.a. reproducibility ** Replication (statistics), the repetition of a test or complete experiment ** Replication crisi ...
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 ...
mechanism is the method of transcription. Translation 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 glands 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 or ...
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 t ...
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 or ...
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 (Moritz Wilhelm) Hugo Ribbert (1 March 1855 in Hohenlimburg – 6 November 1920 in Bonn) was a German professor of pathology. Ribbert studied at Bonn, Berlin and Strassburg. In 1883 he was appointed Professor extraordinarius at Bonn. In 1892 ...
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 Thomas Huckle Weller (June 15, 1915 – August 23, 2008) was an American virologist. He, John Franklin Enders and Frederick Chapman Robbins were awarded a Nobel Prize in Physiology or Medicine in 1954 for showing how to cultivate poliomyelitis ...
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 rete ...
* Human cytomegalovirus


References


External links


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