Human cytomegalovirus (HCMV) is a widespread human virus that infects a large proportion of the global population and, after primary infection, persists in the host organism for life (Whitley, 1996). Although it usually asymptomatic in healthy individuals, in people with a weakened immune system it can cause life-threatening infections, while in immunologically immature newborns it can cause congenital disease with severe consequences that may last a lifetime. HCMV infection is the most common viral congenital infection, with an annual incidence of 0.1–2% (Britt, 2010), and causes more deaths and permanent impairments in newborns than Down syndrome, fetal alcohol syndrome, or neural tube malformations (Ross, Dollard et al., 2006). In addition, HCMV infection is an important cause of organ rejection in transplant patients.
Although HCMV has been studied for decades, there is no effective vaccine, and therapeutic options are limited, toxic, and not universally effective against all viral strains (Andrei, De Clercq et al., 2009). The main reasons for this are: (1) species specificity, which means that HCMV cannot be studied directly in experimental animals; and (2) insufficient understanding of viral genes and their interactions with host genes. Today, this limitation is partly addressed through the use of other cytomegaloviruses, especially murine cytomegalovirus (MCMV), which is genetically and biologically very similar to HCMV.
HCMV belongs to the herpesvirus family. Most people are infected with at least one herpesvirus, and this infection lasts for life. The name comes from the Greek word herpein, meaning “to creep,” which describes the lesions characteristic of some herpesviruses, as well as their ability to cause recurrent infections.
The herpesvirus family is divided into three subfamilies: alpha-, beta-, and gamma-herpesviruses (Whitley, 1996). The best-known herpesvirus is herpes simplex virus type 1 (HSV-1), the causative agent of skin lesions commonly referred to as herpes. Another well-known alpha-herpesvirus is varicella zoster virus, the causative agent of chickenpox. HCMV belongs to the beta-herpesviruses, while Epstein–Barr virus, the causative agent of mononucleosis, and Kaposi’s sarcoma-associated virus belong to the gamma-herpesviruses. The name cytomegalovirus comes from the Greek words cyto, meaning “cell,” megalo, meaning “large,” and virus, describing the typical appearance of infected cells, which are enlarged and rounded.
Herpesvirus infection can develop in two forms: lytic or latent infection. Lytic infection leads to lysis, or destruction, of the infected cell and the production of a large number of new viral particles. By contrast, in some cell types the virus enters a latent form, in which cell lysis does not occur, new viruses are not produced, and only a small portion of viral genes remains active. In this state, the virus is ‘largely escapes detection by the immune system’.
The ability to enter latency is one of the reasons why herpesviruses cause lifelong infections. Another important factor is their ability to evade the immune surveillance. HCMV has a large genome encoding nearly 200 genes, a large proportion of which are dedicated precisely to evading the immune response. Research on this virus has made a significant contribution to understanding how the immune system functions.
For all these reasons, as well as because of the significant impact this virus has on newborns and immunosuppressed patients, research within the Centre of Excellence is focused on better understanding CMV and developing methods by which its properties could be used for therapeutic purposes.
