Diagnosis of Latent Phase in Cytomegaloviral Infections

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Diagnosis of Latent Phase in Cytomegaloviral Infections

Key advantages
  • PCR-based diagnostic test for latent phase Cytomegaloviral infections
  • A novel target for direct immunotherapy/vaccine against latent CMV

Background

Human cytomegalovirus (CMV) is a species specific beta herpes virus that represents significant dangers for neonates and immunosupressed individuals.

This is particularly true in allograft transplant patients and people living with HIV/AIDS. While CMV infection rarely causes severe disease in healthy people, it represents significant problems of morbidity and mortality following reactivation in immunocompromised, foetal and neonatal patients.

It is estimated that 30–60% of bone marrow/organ transplant patients are affected by CMV. The cost of treatment and the consequences of CMV infection in the United States alone is more than US$4 billion per year.

Current therapeutic approaches typically include the antiviral drug Ganciclovir with or without G-CSF (to combat possible antiviral-induced neutropenia associated with this therapy).

It is effective against reactivation of the viral infection, but does not address latent infection where the virus cannot be detected by the patient’s immune system.

There is a need to improve the current therapeutic approach to both productive/reactivation disease, and to target latent infection and detect latency in donors.

During the infectious stage of its lifecycle, CMV is known to produce a viral homolog of the cytokine IL-10, which is a known immunosuppressive factor leading to a dampening of the host’s response to infection.

The invention

Southern blot of mobilized peripheral blood samples (MPB1-MPB4) after hemi-nested PCR amplification

Southern blot of mobilized peripheral blood samples (MPB1-MPB4) after hemi-nested PCR amplification using specific primers. The arrow indicates the position of a predicted 171 bp spliced UL111.5A-region transcript product. A negative control containing no RNA template and a 100 bp DNA ladder (M) are indicated. The presence (+) or absence (-) of reverse transcriptase (RT) in each reaction mixture is indicated.

Researchers at The University of Sydney have identified a novel RNA transcript of this homolog protein called latency-associated cmvIL-10 (LA-cmvIL-10), expressed during the latent phase of infection of myeloid progenitor cells.

Furthermore, LAcmvIL-10 protein has the capacity to interfere with the expression of a critical host immune molecule (MHC class II), which plays a pivotal role in the generation of anti-viral immune responses to control CMV infection.

Further studies have demonstrated an ability to identify latently infected mononuclear cells from putatively identified sero-positive allograft donors. This diagnostic potential presents a significant opportunity.

If the expressed form of the transcript protein can be sequestered then there is potential for the immune system to target the latent virus facilitating its clearance. LA-cmvIL 10 may also represent a possible target for directed immunotherapy.

Principal inventors

  • Dr. Barry Slobedman
  • Dr. Allison Abendroth
  • Dr. Christina Jenkins

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