Cytomegalovirus

Cytomegaloviruses (CMVs) are a distinct subgroup of herpesvirus and are classified as subfamily Betaherpesvirinae in the Herpesviridae family. CMV forms a characteristic nuclear inclusion, which gives an “owl's eye” appearance to infected cells. Many animal species have their own species-specific CMV.

Human CMV maintains a collinear genomic organization, but no significant nucleotide sequence homology with other animal CMVs. Human CMV is also designated as human herpes virus 5 (HHV-5). A great majority of the human population are infected with CMV, without any symptoms by adulthood. CMV is excreted in the urine of infants and intermittently in saliva of healthy seropositive adults. Human CMV may cause diseases such as congenital cytomegalic inclusion disease and infectious mononucleosis. The importance of human CMV as a pathogen has been increasingly correlated with the rising number of immunodeficient patients due to immunosuppressive therapy after transplantation, acquired immune deficiency syndrome (AIDS), and so on.

Mature virions of CMV are 150 to 200 nm in diameter and have an envelope composed of a lipid bilayer and viral glycoproteins. Inside the envelope, a tegment or matrix surrounds an icosahedral capsid, which contains a double-stranded, linear DNA genome. Two types of noninfectious particles, in addition to infectious virions, are produced in cells infected with human CMV. Dense bodies do not contain nucleocapsid or viral DNA and are essentially enveloped tegment protein. Noninfectious enveloped particles have a capsid but no electron-dense DNA core.

 Equine CMV has a genome of 180 kbp, while the genomes of human, simian, and murine CMVs are 230 to 240 kbp. Human CMV is unique among animal CMVs in that it has a genome structure similar to herpes simplex virus 1 (HSV-1, class E structure). Two unique sequences (UL and US) are flanked by inverted repeats. Inversion of the UL and US segments mediated by inverted repeats can give rise to four different genomes. Other animal CMVs are less complicated in genome structure, and genome inversion is not known for them.

 The genome of the AD169 strain of human CMV has been sequenced. Two hundred and eight open reading frames (ORFs) with a coding capacity of at least 100 amino acid residues were identified in the genome. Although only a few of these ORFs have been actually shown to encode proteins, at least 40 have been shown to be dispensable for replication. ORFs have been designated by their location with regard to the unique and repeated sequences (TRL, UL, IRL, IRS, and US) and sequential numbers. By analogy to HSV-1, roughly one-quarter of these ORFs are predicted to encode proteins required for DNA replication and metabolism functions, and three-quarters for virion maturation and virion structure.

 Human CMV shows a highly restricted host range and takes 48 to 72 h to yield detectable amounts of progeny virions. Primary human differentiated cells, such as skin or lung fibroblasts, as well as chimpanzee cells, support human CMV replication, but undifferentiated, transformed, or aneuploid cells are usually nonpermissive for CMV replication. The genes of CMV have been classified into three sequential, kinetic classes: a(immediate early), b(delayed early) and g(late) genes. Expression of the latter two relies on the a gene products. The b gene products mainly serve DNA replication and metabolism, while g gene products encode structural proteins.