Leen De Bolle

Update on Human Herpesvirus 6 Biology, Clinical Features, and Therapy

SUMMARY Human herpesvirus 6 (HHV-6) is a betaherpesvirus that is closely related to human cytomegalovirus. It was discovered in 1986, and HHV-6 literature has expanded considerably in the past 10 years. We here present an up-to-date and complete overview of the recent developments concerning HHV-6 biological features, clinical associations, and therapeutic approaches. HHV-6 gene expression regulation and gene products have been systematically characterized, and the multiple interactions between HHV-6 and the host immune system have been explored. Moreover, the discovery of the cellular receptor for HHV-6, CD46, has shed a new light on HHV-6 cell tropism. Furthermore, the in vitro interactions between HHV-6 and other viruses, particularly human immunodeficiency virus, and their relevance for the in vivo situation are discussed, as well as the transactivating capacities of several HHV-6 proteins. The insight into the clinical spectrum of HHV-6 is still evolving and, apart from being recognized as a major pathogen in transplant recipients (as exemplified by the rising number of prospective clinical studies), its role in central nervous system disease has become increasingly apparent. Finally, we present an overview of therapeutic options for HHV-6 therapy (including modes of action and resistance mechanisms).

Human herpesvirus 6 infection arrests cord blood mononuclear cells in G2 phase of the cell cycle

We here report that after infection with human herpesvirus 6A, human cord blood mononuclear cells accumulate in G2/M phase of the cell cycle. Experiments with foscarnet or ultraviolet (UV)‐irradiated virus stocks pointed at an (immediate‐)early, newly formed viral protein to be responsible for the arrest. At the molecular level, p53, cyclin B1, cyclin A and tyrosine15‐phosphorylated cdk1 accumulated after HHV‐6A infection, indicating an arrest in G2. However, no change was observed in the levels of downstream effectors of p53 in establishing a G2 arrest, i.e. p21 and 14‐3‐3σ. We thus conclude that the HHV‐6A‐induced G2 arrest occurs independently of p53 accumulation.

Productive Infection of Primary Macrophages with Human Herpesvirus 7

ABSTRACT Here we demonstrate replication of human herpesvirus 7 (HHV-7), a T-lymphotropic virus, in macrophages. Productive replication was lost after 2 weeks, but HHV-7 DNA was detected up to 1 month after infection. Thus, macrophages become infected by HHV-7 and might play an important role as a viral reservoir, as has been demonstrated for human immunodeficiency virus type 1.