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Cytomegalovirus

What is CMV?

Human cytomegalovirus (HCMV) is a wide-spread human virus that infects a major portion of human population and after primary infection remains in its host for life (Whitley 1996). Although in healthy persons it does not cause any problems, in immunosuppressed patients it can cause life-threatening infections while in immunologically immature newborns it may cause devastating congenital disease with life-long consequences. In fact, HCMV is the most frequent viral cause of congenital infections with and with annual prevalence of 0.1-2% among newborns (Britt 2010). Deaths and permanent disabilities associated with congenital CMV infection affect more newborns than Down’s syndrome, fetal alcohol syndrome, or neural-tube defects (Ross, Dollard et al. 2006). In transplant patients HCMV is a mayor cause of transplanted organ loss.

Despite its importance in human health and decades of research, effective vaccine is not available while treatment options are scarce, toxic and not effective against all virus strains (Andrei, De Clercq et al. 2009). Major obstacles to progress in vaccine and antiviral drug development are (1) species specificity of HCMV that prevents the use of HCMV in animal models, and (2) gaps in our understanding of viral genes and their interaction with host genes. First limitation is circumvented by the use of model animal viruses, especially murine cytomegalovirus (MCMV) which shares numerous similarities to HCMV.

CMV is a herpesvirus

HCMV belongs to the family of viruses called herpesviruses. Most of the human population is infected with at least one herpesvirus and the infection lasts for life. Herpesviruses derive their name from the Greek word herpein, which means to creep and reflects the spreading of the skin lesions and the propensity of these viruses to cause recurrent infections.

Family of herpesviruses contains 3 subfamilies: alpha, beta and gamma herpesviruses (Whitley 1996). Certainly the most well-known of all herpesviruses is an alpha-herpesvirus Herpes simplex virus 1 (HSV-1) that causes skin lesions. Varicella zoster virus, the causative agent of chicken-pox is another alpha-herpesvirus. HCMV belongs to beta-herpesviruses whereas, while Epstein-Barr virus (EBV) that causes mononucleosis and Kaposi’s sarcoma-associated virus (KSHV)are gamma-herpesviruses.

Cytomegalovirus derives its name from three words: cyto meaning cell, megalo meaning large and virus. The name aptly describes cellular pathology of CMV infected cells: large and rounded cells.

CMV biology

Infection with a herpesvirus can have two outcomes: lytic or latent infection. Lytic infection results in a lysis of an infected cells and generation of numerous new viral particles. In certain cell types, however, the virus enters latent infection where the viral genome remains dormant, only a fraction of viral genes is expressed and no new viral progeny is made. Such virus is invisible to the immune system. This ability to enter latency has made herpesviruses such successful life-long persistent pathogens.

Another reason lies in this virus’ ability to evade every arm of our immune system. HCMV possesses a relatively large genome which encodes nearly 200 genes and a major portion of those genes are dedicated towards immune evasion. By studying CMVs, we have also learned a great deal about our immune system. Because of this and huge importance this virus has on most vulnerable members of our society, newborns and immunosuppressed patients, several workpackages of this Center of excellence are dedicated towards better understanding of this virus as well as developing methods to use this virus’ abilities to work for us instead against us.