HCMV Antivirals and Strategies to Target the Latent Reservoir

Abstract

Human cytomegalovirus (HCMV) is a ubiquitous human herpesvirus. In healthy people, primary infection is generally asymptomatic, and the virus can go on to establish lifelong latency in cells of the myeloid lineage. However, HCMV often causes severe disease in the immunosuppressed: transplant recipients and people living with AIDS, and also in the immunonaive foetus. At present, there are several antiviral drugs licensed to control HCMV disease. However, these are all faced with problems of poor bioavailability, toxicity and rapidly emerging viral resistance. Furthermore, none of them are capable of fully clearing the virus from the host, as they do not target latent infection. Consequently, reactivation from latency is a significant source of disease, and there remains an unmet need for treatments that also target latent infection. This review briefly summarises the most common HCMV antivirals used in clinic at present and discusses current research into targeting the latent HCMV reservoir.

Keywords: F49A-FTP; antiviral; human cytomegalovirus; latency; latent reservoir; shock and kill; transplant.

Figure 1

Opportunities for purging the latent reservoir (a) Seropositive donors could be treated before they donate organs/tissue to purge cells latently infected with HCMV. Seropositive recipients could likewise be treated prior to immunosuppression to remove their own existing latently infected cells that could reactivate. (b) Organs could be treated in isolation in ex vivo perfusion systems to remove latently infected cells from seropositive donors.