Cytomegalovirus – Walking Dead

How did I get to 45 years of age and not ever hear of this? ~

Infects 60-90% of the population worldwide. Typically asymptomatic. W.T.Fungal?

infection in immunocompromised individuals life threatening.

Infection in utero: Leading cause of infectious disease related birth defects. 1 in 100 infected. Again…W.T.Fungus?

  1. Mild to severe hearing loss.
  2. Cognitive deficits(ADHD, Autism?)
  3. Physical abnormalities.

Human cytomegalovirus (HCMV  or Human herpesvirus 5) is a large DNA virus (>235 kb) that belongs to theBetaherpesvirinae genus of the Herpesviridaefamily. Primary HCMV infection in immunocompetent individuals is usually benign but establishes a lifelong latent state. Immune suppressed transplant recipients or AIDS patients are particularly susceptible to life-threatening end-organ disease. The other vulnerable population is the developing fetus in utero. During pregnancy, the vertical transmission of the virus across the placenta to the fetus (congenital infection) can lead to serious symptomatic disease in newborns that include mental retardation and deafness. Congenital CMV is the leading cause of mental retardation/deafness in newborns with over 5,000 children each year in the US. HCMV is also considered to be a contributing factor to vascular disease and specific cancers (eg. glioblastoma).

Cytomegalovirus-Mother to Child Invasion

Anatomy of the maternal-fetal interface, where the fetus-derived placenta attaches to the mother’s uterus. The basic structural unit of the placenta is the chorionic villus, composed of a stromal core with blood vessels, surrounded by a basement membrane, and overlaid by cytotrophoblast stem cells. As part of their differentiation pathway, stem cells detach from the basement membrane and adopt one of two lineage fates. They fuse to form the syncytiotrophoblast, which covers floating villi, or they join a column of extravillus cytotrophoblasts that invade the uterine stroma. The syncytiotrophoblast mediates nutrient and gas exchange across the maternal-fetal interface. The anchoring villi (AV) establish physical connections between the mother and fetus through the attachment of cytotrophoblast columns. The floating villi (FV), bathed by maternal blood, contain the fetal capillaries (zone I). Cytotrophoblasts in the AV attach the placenta to the uterine wall (zone II). Cytotrophoblasts then invade the decidua up to the first third of the myometrium (zone III), anchoring the placenta to the uterus and gaining access to the maternal circulation. Sites proposed as routes of CMV infection in utero are numbered 1 to 4.

An Institute of Medicine report placed a vaccine to cytomegalovirus as a high priority for vaccines for the 21st century and various vaccine strategies are being investigated. An alternative intervention therapy, in lieu of a vaccine against HCMV, is the use of antivirals. Licensed antivirals are available for the treatment of transplant and AIDS patients. These drugs act at late stages of the virus life cycle and can lead to the development of resistant strains.  There is an additional risk to the fetus of toxic side effects from extended drug therapy. Importantly, we have recently demonstrated in a novel humanized chimeric animal model that antiviral ganciclovir (the most commonly used HCMV antiviral for transplant patients) will reduce but not prevent congenital infection. Consequently, a vaccine against HCMV would be the best intervention strategy.