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HCMV is present in humans with seroprevalence ranging from 45 to 96% globally (about 96% in China). HCMV infection occurs throughout the body, is always mild and asymptomatic in healthy populations, but is symptomatic or even lethal in immunocompromised/immune-immature people, such as HIV-infected patients, transplant recipients and new-borns infected in utero. The virus can enter latency after primary infection, but can be re-activated at any time.
In the general population, the immune system restricts HCMV infection to latency and is asymptomatic. However, HCMV infection causes severe diseases in immune-immature and immune-compromised patients. This includes transplant recipients, who often suffer severe complications including pneumonia, hepatitis and gastrointestinal ulcerations after transplantation. This is a consequence of their impaired immune system which allows the latent HCMV infection to be reactivated. Consequently, transplant recipients always receive pre-emptive or prophylactic antiviral therapy but nevertheless have a high risk of developing drug resistance and HCMV reactivation.
To date, no effective vaccine is available for HCMV, and only four licensed drugs (ganciclovir/valganciclovir, cidofovir and foscarnet, which all target viral DNA replication) are available. Most recently, in the US in 2017, letermovir, which targets viral DNA packaging, was licenced for prophylaxis in bone marrow patients. However, all of these drugs can cause severe side effects and, in the long-term, drug resistance inevitably occurs due to accumulation of mutations in the HCMV genome. In spite of these problems, HCMV drug resistance has not been well characterized, leaving a huge gap in options for clinical therapy and treatment.
HCMV studies to date have primarily been experimental and have used “classical” approaches to identify key proteins and clarify their roles in the infection process. Computational methods can assist in genome characterization and is widely used in the study of other viral and bacterial genomes, but this approach has not been widely adopted in the investigation of the HCMV genome. We are developing computational methods to perform genome wide comparison of HCMV strains, including both coding and non-coding (miRNA) regions. In this work, we collaboratiing with the lab of Luo Minhua in Wuhan Institute of Virology and hospitals in Beijing and Changsha who have been collecting viral isolates from transplant patients. This work is supported by a Scientia Fellowship from UiO
