LIVING THE LAB LIFE
A BLOG FOR ASCLS REGION V
This week, NPR featured a news article about a young boy born with serious birth defects due to CMV infection. While Zika has been a hot topic in the news for the past couple of years due to the potential devastating birth defects associated with infection, CMV has a record of doing much more damage. While CMV has flown under the radar for most in the general population, as laboratorians, CMV is an ever-present part of our world. We may perform testing on obstetric patients, tittering out IgM and IgG antibodies to evaluate for current, recurrent, or past infection. We may see the cytopathic effects of CMV upon microscopic examination of tissue specimens. Or we transfuse CMV-negative blood products to vulnerable populations. Here I will discuss the virus further in depth.
Human cytomegalovirus, or CMV, is a member of the Herpesviruses family, along with other well-known viruses like herpes simplex virus types 1 and 2, Epstein-Barr, and varicella-zoster. The Herpesviridae are large, complex, double-stranded DNA viruses. The hallmark of this family of viruses is their ability to establish latent infections and re-emerge periodically throughout the life of their host. In the case of CMV, the virus establishes latency by residing in monocytes.
About half of all people in the human population developed nations are infected with CMV. At any given time, 10% of people are shedding the virus, either through tears, urine, saliva, stool, semen, cervical secretions, or breast milk. The virus is commonly transmitted via sexual and oral routes, but is also transmitted through blood transfusions, tissue transplants, in utero. In adults, CMV is often an asymptomatic, benign infection. Some cases present like the common cold, or a less severe mononucleosis-type disease (remember the causative agent of mononucleosis is another member of the Herpesviruses family, EBV).
CMV is the most common congenital infection in the United States, occurring in approximately 1% (0.5 – 2.5%) of all live births or 30,000-40,000 cases per year. 10% of infected babies show signs of disease, with mental retardation and hearing loss being the most common presentations. Of this 10% that show signs of infection at birth, 90% will go on to have neurological abnormalities later in life. In the most severe cases, CMV-infected babies may be stillborn or die shortly after delivery. If a mother is infected for the first time while she is pregnant, that increases the likelihood of serious birth defects in the baby.
CMV also can cause serious infection in immunosuppressed patients, like those undergoing immunosuppressant therapy post-organ transplant and AIDS patients. Leukoreduction and irradiation of blood products helps to prevent transmission of CMV through blood transfusions, which is of importance in newborns and the immunosuppressed. CMV is also important in transplant medicine, as CMV is believed to play a role in graft rejection by causing vasculopathy. This occurs in cases where the transplanted tissue is CMV-positive but the transplant recipient is CMV-negative. In these cases, treating the transplant recipient with a CMV anti-viral agent reduces the risk of transplant rejection.
Specific immunoassays are available to titer CMV IgM and IgG levels in serum. CMV IgM levels can rise during a reactivation phase, making it difficult to the determine a primary infection. PCR and other molecular techniques can be used to detect CMV in blood, tissue, urine, and respiratory specimens; normally sterile body fluids are the best for detection of CMV. ELISA and immunofluorescence methods are available to detect CMV specific viral antigens. Urine is the most frequently used source to diagnose CMV infection in newborns; the sample should be collected within two weeks of birth.
Cell culture of CMV is done using human fibroid cell lines. It can take up to six weeks for cytopathic effects to be visible in standard cell methods, due to the slow replication cycle of the virus. The use of shell vial methods can cut that turnaround time down to as little as one day.
In biopsies, the cytomegalic cell (enlarged cell with a dense, central, basophilic intranuclear inclusion body) can be visualized. These cells are believed to be epithelial in nature and are readily visualized by hematoxylin-eosin and Papanicolaou stains.
Mahon, C. R., Lehman, D. C., & Manuselis, G. (2011). Textbook of Diagnostic Microbiology (4th ed.). Maryland Heights, Missouri: W.B. Saunders Company.
Murray, P. R., Rosenthal, K. S., & Pfaller, M. A. (2009). Medical Microbiology (6th ed.). Philadelphia: Mosby Elsevier.
Neighmond, P. (2017, March 27). For Gideon, Infection with Common Virus Caused Rare Birth Defects. Retrieved March 28, 2017, from NPR: http://www.npr.org/sections/health-shots/2017/03/27/520966988/for-gideon-infection-with-a-common-virus-caused-rare-birth-defects
Norkin, L. C. (2010). Virology: Molecular Biology and Pathogenesis. Washington, DC: ASM Press.