Human cytomegalovirus (CMV, also called Human herpesvirus 5) is a member of the herpes virus family and shares the characteristic ability to remain latent within the body for life within an infected individual. Although a CMV infection is typically asymptomatic in healthy persons, immunocompromised individuals such as AIDS patients, organ transplant recipients and newborn infants, are at high-risk of developing life-threatening complications from primary infections and reactivations. Most people (85%) have been infected by CMV by 40 years of age.
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CMV is not considered highly contagious and the virus is generally passed through direct contact with body fluids, such as urine, saliva, breast milk, transplanted organs and blood transfusions. Healthy pregnant women are not at special risk for disease from CMV infection but between 5-8% are infected for the first time during their pregnancy, and this can lead to serious complications. Among infants born with CMV infection (congenital CMV), about 20% will have permanent disabilities. There is no vaccine available to protect against CMV and public health measures focus on reducing the risk of CMV transmission to pregnant women, women of childbearing age and other people at risk of more serious infections.
Congenital Cytomegalovirus (CMV) refers to a group of symptoms that occur when an infant is infected before birth and it is the most common cause of congenital viral infections worldwide. Only 10% of congenitally infected newborns display abnormalities at birth, however 80% – 90% will develop complications within the first few years of life. Symptoms of congenital CMV include hearing loss, vision impairment, and varying degrees of mental retardation. The risks for a fetus becoming infected by CMV appear to be almost exclusively associated with women who are having a primary infection during pregnancy. There appears to be little risk of CMV related complications for women who have been infected at least 6 months prior to conception.
Various diagnostic tests have been developed to detect a CMV infection including viral culture, serological assays, PCR analysis and cytopathology. The pp65 antigenemia test, in which a monoclonal antibody against CMV pp65 is used to detect a major CMV matrix protein (pp65) in leukocytes, has the longest history in clinical use. However, it has been criticized for its subjectivity in reading positive results, time consuming and intricate procedures, difficulty in standardization, and a need for sufficient leukocytes. The ELISA IgG/IgM assay which measures antibodies to CMV, specifically CMV IgM, IgG and IgG avidity, has become the most commonly available serologic test. The detection of IgM is indicative of an acute or primary infection whereas the detection of IgG is indicative of a past infection. In the case where both IgM and IgG can be detected, the level of IgG avidity can help distinguish between an acute infection and a past infection. For this reason, newer assays have begun to incorporate the detection of anti-CMV IgM together with determination of the avidity index of anti-CMV IgG. To improve the sensitivity and specificity of CMV antibody detection, immunogenic CMV proteins have been studied and characterized during the past two decades and over 15 structural polypeptides have been identified in a natural infection. The combination of antigens selected is the most critical element affecting assay sensitivity and specificity.
The most suitable proteins are reportedly:
• CMV pp150: a tegument phosphoprotein detectable during both latent and re-activated infections. During primary infection the antibody response to pp150 may be delayed.
- CMV pp52: the major DNA binding protein, nonstructural nuclear phosphoprotein which is regarded as an early marker of seroconversion
- CMV pp65: major structural phosphoprotein (lower matrix) and main component of extracellular virus particles. The antibody response is detectable during early infection only
- CMV gB Antigen: a membrane glycoprotein which is the most abundant component of the viral envelope and a target of neutralizing antibodies
- CMV pp38: structural protein suggested to be an important immunodominant protein in early infection. Evidence also suggests that CMV-IgM detection against viral structural proteins (pp150 and pp38) are a valuable parameter for the early diagnosis of a recurrent CMV infection. Several diagnostic manufacturers have incorporated a combination of CMV lysate and CMV recombinant proteins to improve assay performance.
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