Discovering how human cytomegalovirus functions during the latent phase of infection

Summary

Human cytomegalovirus functions during latent infection of myeloid cells

Supervisor(s)

Associate Professor Barry Slobedman, Associate Professor Allison Abendroth

Research Location

Westmead - Westmead Millennium Institute

Program Type

PHD

Synopsis

We have also discovered that CMV expresses a number of viral genes during the latent phase of infection, including those that encode immunosuppressive properties. We hypothesise that viral genes expressed during the latent phase of infection are likely to encode functions which enable the virus to successfully persist within the human host. Therefore, viral genes identified as playing an important role in latency would serve as ideal targets for the development of therapies aimed at reducing the devastating disease resulting from reactivation of latent virus in immunosuppressed individuals. This project will examine the functions of viral genes expressed by CMV during viral latency using a number of molecular and cellular biology approaches. This project also has the potential to examine the impact of latent infection on host cell gene expression, to address the hypothesis that CMV orchestrates an environment within the host cell that enhances the capacity of this virus to successfully remain within the host in a latent state (from which it can reactivate years later under conditions of immunosuppression to cause life-threatening disease).

Additional Information

What is human cytomegalovirus?

  • Human cytomegalovirus (CMV) is a medically important virus that affects millions of people worldwide
  • CMV is a member of the Herpesvirus family of viruses
  • CMV is carried by the vast majority of the human population (up to 90%)
  • Most people become infected in the first few years of life, or in their adolescent years
  • Once infected, the virus remains in your body for the rest of your life
The good news...
  • Infection usually causes mild or asymptomatic disease in most healthy adults
The bad news...
  • CMV infection is the most common congenitally acquired infection in infants where it is the leading viral cause of neurological defects eg mental retardation, deafness.
  • CMV is a major cause of life-threatening disease in immunocompromised individuals including AIDS patients and allogeneic transplant recipients. Infection during immunosuppression results in disseminated CMV which can lead to severe infections of the GI tract, hepatitis, pneumonia, accelerated atherosclerosis, rejection in solid organ transplant recipients and graft-versus-host disease in bone marrow recipients.
CMV life cycle: 3 distinct phases
  1. Productive infection: This is characterised by the synthesis of new infectious virus, resulting in death of the host cell.
  2. Latent infection: Following primary infection, CMV can enter into a latent (or dormant) state during which time infectious virus is not produced. The latent phase of infection lasts for the life of the host. The immune system is unable to clear this latent infection. Despite its importance to human disease, the mechanisms underlying latency are very poorly understood
  3. Reactivation: Reactivation is the process by which the virus transitions from a latent state back to a productive infection state. This results in shedding of virus in saliva, urine or other body secretions. Reactivation from latency causes most of the serious CMV disease in immunocompromised individuals such as transplant recipients. There is no vaccine, drug or treatment that prevents or interrupts viral latency, nor is it known how the virus is able to establish latency to successfully persist within the human host
The types of techniques you will likely use: Flow cytometry, RNA extraction and PCR-based detection techniques, protein expression, immunofluorescent staining and confocal microscopy, western blotting, cloning, transfection of cells, mammalian cell culture and virus culture. Funding: Tax-free, supplementary (top-up) funds are available to individuals who are able to attract scholarship funding.

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Keywords

Human cytomegalovirus, post-transplant disease, Leukaemia, Virology, Latent infection, Pathogenesis, Herpesvirus, Immune modulation, Infectious diseases, Infection & immunity, Cell biology, transplantation, Congenital infection

Opportunity ID

The opportunity ID for this research opportunity is: 255

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