Scientists at the Institute of Animal Reproduction and Food Research of the Polish Academy of Sciences in Olsztyn are investigating the mechanism of long-term infection of the fetus with cytomegalovirus. The virus is usually harmless for healthy people. The problem arises in immunocompromised patients and pregnant women, as it crosses the placenta and can cause serious congenital diseases.
– We are investigating the molecular basis for establishing long-term cytomegalovirus infection in neural cells. We hope to find out the factors responsible for the persistence of the virus in neural cells, and thus identify the causes of the observed damage to the nervous system associated with cytomegalovirus-induced congenital disease – emphasises Dr Magdalena Weidner-Glunde, leader of the research project and head of the Molecular Microbiology and Virology Laboratory of the IARFR PAS in Olsztyn.
THE DORMANT VIRUS
Human cytomegalovirus (HCMV) infection is very common, with more than 80 % of the Polish population infected. The primary infection in healthy people is usually asymptomatic or shows the symptoms of a slight cold, but in immunocompromised patients, e.g. after transplantation (when immunity is deliberately lowered to prevent transplant rejection) or those with AIDS, it can cause serious illness.
– HCMV is also a cause of congenital disease, as the virus is able to pass from the bloodstream of the infected mother through the placenta to the fetus. The disease resulting from congenital cytomegalovirus infection is associated with infection of the central nervous system and consequent sensory-nervous damage. Symptoms associated with HCMV congenital disease can include hearing loss, visual impairment or even intellectual disability, explains the researcher.
The herpesviruses (such as herpes virus and chickenpox virus), once they enter our body, remain in our body for the rest of our lives. The response of our immune system to their presence – i.e. antibodies – can be detected by laboratory blood tests. They also allow us to determine whether a person has an active or latent infection.
In fact, the life cycle of herpesviruses comprises two phases: a latent (dormant) phase, from which the virus occasionally 'wakes up’ to enter the active (lytic) phase. – In the lytic phase, the virus actively multiplies by producing a large number of new viral particles. In contrast, in latency, viral protein synthesis is reduced to a minimum and there is no production of new viral particles, which prevents our immune system from effectively detecting the infection – explains Magdalena Weidner-Glunde.
HCMV has a circular genome (episome) that, during latent infection, has the ability to attach to host chromosomes and thus ensure the persistence of infection. – In other herpesviruses, it is known which protein is responsible for this binding of the viral genome to chromosomes. In the case of cytomegalovirus, we do not yet know this. In our research, we are investigating whether the viral protein IE1 is involved in the binding of the genome to the chromosomes and thus – determines the survival of the virus. Analysing the function of this protein will allow us to learn and understand how it is possible for the cytomegalovirus genome to survive in the cell for such a long time – points out Magdalena Weidner-Glunde.
LEARN THE DIFFERENCES IN CELL TYPES
Cytomegalovirus particles have different properties in terms of infection and multiplication in different cell types. So far, cytomegalovirus has been studied in its latent phase mainly in haematopoietic stem cells (from which, for example, red blood cells can arise). Recently, it has been shown that long-term HCMV infection can also take place in neural precursor cells (from which, for example, neurons are later formed). Long-term infection in these cells may be responsible for the sensory-neural damage that is symptomatic of HCMV-induced congenital disease.
Scientists from Olsztyn are also looking into comparing the mechanism of long-term virus infection in the two cell types in order to understand the differences and how cytomegalovirus disrupts the functioning of different cell types.
– For the active phase of virus infection, drugs are given to inhibit viral replication. However, there are still no drugs for the latent phase to help simply get rid of it. The results of our study will therefore be able to contribute not only to the understanding of the pathogenesis of congenital cytomegalovirus infections, but also to help develop new therapies – concludes the scientist. The research – led by Magdalena Weidner-Glunde, PhD – is being conducted as part of a project entitled “Exploring mechanisms of congenital human cytomegalovirus infection: replication, spread and latency establishment”, funded by more than PLN 3 million from the National Science Centre. The project is expected to end in May 2024.