Cytomegalovirus (CMV) - Medscape Reference

Cytomegalovirus (CMV) is a double-stranded DNA virus and is a member of the Herpesviridae family. The other family members include herpes simplex virus type 1 (HSV-1 or HHV-1) and herpes simplex virus type 2 (HSV-2 or HHV-2), varicella zoster virus (VZV), human herpes virus (HHV)–6, HHV-7, and HHV-8. CMV shares many attributes with other herpes viruses, including genome, virion structure, and the ability to cause latent and persistent infections. CMV has the largest genome of the herpes viruses. Replication may be categorized into immediate early, delayed early, and late gene expression based on time of synthesis after infection. The DNA is replicated by rolling circles. Human CMV grows only in human cells and replicates best in human fibroblasts.

At least 50-60% of the US population has been exposed to CMV, [3] with a prevalence of more than 90% in high-risk groups (eg, male homosexuals), and outside of the US prevalence can be more than 90%. [4, 5, 6] The prevailing age of infection varies worldwide. In developing countries, most infections are acquired during childhood, whereas in developed countries, up to 50% of young adults are CMV seronegative. The incidence of CMV seropositivity rises with age and in a US-based study was reported to increase from 36% in children aged 6-11 years to 91% in individuals older than 80 years. [7] Other factors associated with CMV seropositivity include ethnicity (77% in Mexican Americans and 71% in Blacks), [8] female sex, foreign-born status, and low socioeconomic status. [8]

CMV usually causes an asymptomatic infection; afterward, it remains latent throughout life and may reactivate. Infection is defined as isolation of CMV, its viral proteins, or its nucleic acid from any tissue sample or body fluid. [9] In immunocompetent individuals, symptomatic disease usually manifests as a mononucleosis syndrome, which was first described in adults in 1965. [10]

Clinically significant CMV disease (reactivation of previously latent infection or newly acquired infection) frequently develops in patients immunocompromised by HIV infection, solid-organ transplantation, or bone marrow transplantation, as well as in those receiving high-dose steroids, tumor necrosis antagonists, or other immunosuppressing medications for conditions such as systemic lupus erythematosus (SLE), rheumatoid arthritis, Crohn disease, or psoriasis, among others. In patients coinfected with HIV, CMV infection leads to progression to AIDS and eventually death, even in those receiving antiretroviral therapy (ART). [11]

Symptomatic CMV disease in immunocompromised individuals can affect almost every organ of the body, resulting in fever of unknown origin, pneumonia, hepatitis, encephalitis, myelitis, colitis, uveitis, retinitis, and neuropathy.

Individuals at an increased risk for CMV infection include individuals who attend or work at daycare centers, patients who undergo blood transfusions, persons who have multiple sex partners, and recipients of CMV mismatched organ or bone marrow transplants.

CMV is transmitted from person to person via close contact with an individual who is excreting the virus. It can be spread through the placenta, blood transfusions, organ transplantation, and breast milk. It also can be spread through sexual transmission.

In the United States, congenital CMV transmission from a mother with acute infection during pregnancy is a significant cause of neurologic abnormalities and deafness in approximately 8000 newborns annually. [12, 13]

Multiple genetically distinct strains of CMV exist. Differences in genotypes may be associated with differences in virulence. Infection with more than one strain of CMV is possible and has been observed in organ transplant recipients. Dual infection is a possible explanation for congenital CMV infection in children of CMV-seropositive mothers.