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 called CMV. Within Herpesviridae, HCMV belongs to the Betaherpesvirinae subfamily, which also includes cytomegaloviruses from other mammals. CMV is a double-stranded DNA virus. Although they may be found throughout the body, HCMV infections are frequently associated with the salivary glands. HCMV infection is typically unnoticed in healthy people, but can be life-threatening for the immunocompromised, such as HIV-infected persons, organ transplant recipients, or newborn infants. Congenital cytomegalovirus infection can lead to significant morbidity and even death. After infection, HCMV remains latent within the body throughout life and can be reactivated at any time. Eventually, it may cause mucoepidermoid carcinoma and possibly other malignancies such as prostate cancer, breast cancer, ovarian cancer and glioblastoma. HCMV is found in all geographic locations and all socioeconomic groups, and infects between 60% and 70% of adults in the first world and almost 100% in the third world. Of all herpes viruses, HCMV harbors the most genes dedicated to altering (evading) innate and adaptive host immunity and represents a lifelong burden of antigenic T cell surveillance and immune dysfunction. Commonly it is indicated by the presence of antibodies in the general population. Seroprevalence is age-dependent: 58.9% of individuals aged 6 and older are infected with CMV, while 90.8% of individuals aged 80 and older are positive for HCMV. HCMV is also the virus most frequently transmitted to a developing fetus. HCMV infection is more widespread in developing countries and in communities with lower socioeconomic status and represents the most significant viral cause of birth defects in industrialized countries. Congenital HCMV is the leading infectious cause of deafness, learning disabilities, and intellectual disability in children. CMV also "seems to have a large impact on immune parameters in later life and may contribute to increased morbidity and eventual mortality."
Signs and symptoms Human cytomegalovirus infection has a classic triad of symptoms: fever, peaking in the late afternoon or early evening; pharyngitis, usually exudative; and symmetrical adenopathy.
Virology
Transmission The mode of HCMV transmission from person to person is unknown, but is presumed to occur through bodily fluids, including saliva, urine, blood, and tears. Cytomegalovirus is most commonly transmitted through kissing and sexual intercourse. It can also be transferred from an infected mother to her unborn child. Infection requires close, intimate contact with a person secreting the virus in their saliva, urine, or other bodily fluids. CMV can be transmitted sexually and via breast milk, and also occurs through receiving transplanted organs or blood transfusions. Although HCMV is not highly contagious, it has been shown to spread in households and among young children in day care centers.
Replication HCMV replicates within infected endothelial cells at a slow rate, taking about five days in cell culture. It also infects fibroblasts, which requires expression of only a trimeric viral receptor complex, rather than the full pentameric complex that is required for infection of endothelial and epithelial cells. Like other herpesviruses, HCMV expresses genes in a temporally controlled manner. Immediate early genes (expressed 0–4 hours after infection) are involved in the regulation of transcription, followed by early genes (expressed 4–48 hours after infection) which are involved in viral DNA replication and further transcriptional regulation. Late genes are expressed during the remainder of infection up to viral egress and typically code for structural proteins. While HCMV encodes for its own functional DNA polymerase, the virus makes use of the host RNA polymerase for the transcription of all of its genes. In disseminated cytomegalovirus infections, as may be seen in the context of an immunosuppressed host, the virus is readily transmitted between polymorphonuclear leukocytes (PM-NLs) and endothelial cells. Infected endothelial cells produce cytokines that attract PM-NLs, which then adhere to the endothelium by interactions between their CD18-containing cell surface integrins and the endothelial-expressed ICAM-1. Microfusions between the cells then take place in a manner dependent on expression of the viral gene locus UL128L. Synthesis of the viral double-stranded DNA genome occurs at the host cell nucleus within specialized viral replication compartments. Nearly 75% of the genes encoded by HCMV strain AD169 can be deleted and still result in the production of infectious virus. This suggests that the virus focuses on avoiding the host immune system for a timely entrance into latency.
At-risk populations CMV infections are most significant in the perinatal period and in people who are immunocompromised.
Pregnancy and congenital infection
HCMV is one of the vertically transmitted infections that lead to congenital abnormalities. (Others are: toxoplasmosis, rubella and herpes simplex.) Congenital HCMV infection occurs when the mother has a primary infection during pregnancy. Up to 5 of every 1,000 live births are infected. Five percent develop multiple disabilities, and develop cytomegalic inclusion disease with nonspecific signs that resemble rubella. Another five percent later develop cerebral calcification (decreasing IQ levels dramatically and causing sensorineural deafness and psychomotor retardation). However, infants born preterm and infected with HCMV after birth may experience cognitive and motor impairments later in life.
Immunocompromised adults CMV infection or reactivation in people whose immune systems are compromised—for example, people who have received transplants or are significantly burned—causes illness and increases the risk of death. HCMV infection involving the gastrointestinal tract represents a leading cause of morbidity and mortality among kidney transplant recipients. Signs and symptoms of the disease may be variable. Prompt anti-viral therapy administration and changes in immunosuppression are key factors for optimizing its management. CMV reactivation is commonly seen in people with severe colitis. Specific disease entities recognized in those people are
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