Bethaherpesviruses in Children Who Are Immune Suppressed

Unexplained fever in children with cancer is a common occurrence, often requiring hospital
admission for evaluation and treatment with intravenous antibiotics. While empiric use of
intravenous antibiotics is the norm in this population, between 48-70% of febrile and
neutropenic episodes remain without an identifiable source. An understudied area is the
potential role of betaherpesvirus infections in such febrile episodes. These viruses are
significant pathogens in patients who become immunocompromised in conjunction with organ
transplantation or acquired immune deficiency syndrome (AIDS). It is possible that they are
similarly pathogenic in children who become immunocompromised due to cancer chemotherapy.

Thus, we will investigate the association between the betaherpesviruses and fever in children
with cancer. The betaherpesviruses include cytomegalovirus (CMV), human herpesvirus 6A
(HHV-6A), human herpesvirus 6B (HHV-6B), and human herpesvirus 7 (HHV-7). These viruses are
grouped based on shared biological and genetic properties. Each is commonly acquired in
childhood, persists in the human host, and can reactivate. Reactivation occurs intermittently
throughout life in healthy individuals and is seldom associated with disease. Immune
suppression is associated with a higher likelihood of reactivation and clinical disease.
Latency of these viruses involves highly regulated processes that result in the viruses
evading destruction and persisting within the host. Should balance be disrupted, as with
cancer and anticancer therapy altering the normal host state, the environment may become
favorable for betaherpesvirus reactivation, leading to disease and further alterations of the
immune system.