Epstein Barr virus (EBV) and Cytomegalovirus (CMV) are both widely spread herpesviruses that infect immune cells and establish latency (in B cells and in cells of the monocytic lineage respectively) in the host after primary infection and they are considered as a part of our “virobiome”. The time-point for infection is associated with socio-economic conditions, and seroconversion occurs comparably late in Westernized countries. Although herpesvirus latency influences the immune system also in the asymptomatic host, the mechanisms behind this are still not very clear. As herpesviruses and man have co-evolved for a long time, several of these virus-induced effects on our immune system could be beneficial or at least confer an immunological imprint that we consider as “normal”. This is relevant to consider today, with the knowledge that the time-point for sero-conversion is more and more delayed, in particular in Westernized countries - is there for example an immunological advantage of an early EBV infection? For EBV, an infection during infancy is usually asymptomatic, but a later infection in adolescence or adulthood is frequently associated with mononucleosis. These age-related differences in symptoms has been ascribed the differences in immune maturation between infants and adults, but is still poorly understood.

We have described that an early EBV-infection (before 2 years of age) is associated with a protection against early and persistent IgE-sensitization, while a later infection is associated with an increased risk (Saghafian-Hedengren et al 2010). The mechanisms behind this possible protection are however also still unknown. Still, both EBV and CMV latency is associated with significant impact on immune parameters in children. We have that early infection (<2years) with EBV and CMV correlates with both adaptive (T cells) and innate (NK cells) function at two years of age (Nilsson et al 2009, Saghafian-Hedengren et al 2009). We have described that age has a significant impact on EBV infection in vitro as well as do a previous CMV infection (Sohlberg et al 2013), but also that EBV can influence how CMV modulates NK cell function in vivo (Saghafian-Hedengren et al 2013). Our most recent work shows a striking delay in EBV and CMV infection in Swedish children and interesting connections between the early gut microbiota and the age of seroconversion, indicating that the degree of immune maturity can influence the time point for infection (Carvalho-Queiroz et al).

We continue to study how these two viruses impacts the immune system in children with studies on both B- and T cell compartments (Carvalho-Queiroz et al, Björkander et al) in order to investigate mechanisms behind how these viruses influence immune maturation in healthy children.

 

References

Sohlberg E, Saghafian-Hedengren S, Rasul E, Giovanna Marchini, Nilsson C, Klein E, Nagy N, Sverremark-Ekström E. Cytomegalovirus-seropositive children show inhibition of in vitro EBV-induced B-cell infection that is associated with CD8+CD57+ T-cell enrichment and IFN-g. J Immunol 2013; 191: 5669-76.

Saghafian-Hedengren S, Sohlberg S, Theorell J, Carvalho-Queiroz C, Nagy N, Nilsson C, Bryceson Y, Sverremark-Ekström E. Epstein-Barr virus co-infection in children boosts cytomegalovirus-related differentiation of Natural Killer cells. J Virol 2013; 87: 13446-55.

Saghafian-Hedengren S, Sverremark-Ekström E, Lilja G, Linde A, Nilsson C. Early life EBV-infection protects against persistent IgE-sensitization. J Allergy Clin Immunol 2010; 125: 433-438.

Saghafian-Hedengren S, Sundström S, Sohlberg E, Nilsson C, Troye-Blomberg M, Berg L, Sverremark-Ekström E. Herpes virus seropositivity in childhood associates with decreased monocyte-induced NK-cell IFN-g production. J Immunol 2009; 182: 2511-2517.  

Nilsson C, Larsson AK, Montgomery SM, Sverremark-Ekström E, Linde A, Lilja G, Troye Blomberg M. EBV and CMV are differentially associated with numbers of cytokine-producing cells and early atopy. Clin Exp Allergy 2009; 39:509-517.