Effect of murine cytomegalovirus infection on haematopiesis and myeloid cell differentiation and function

Andrea Khong

Research output: ThesisDoctoral Thesis

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[Truncated] Cytomegalovirus (CMV) is a ubiquitous pathogen affecting over 95% of the world’s population. While infection is typically asymptomatic in healthy individuals, the virus persists life-long in its host and can be reactivated following withdrawal of immune control. As such, it remains a serious clinical concern in individuals who are immunocompromised, such as newborns and neonates, transplant and/or chemotherapy recipients, and HIV/AIDS patients. CMV also has the ability to cause immunosuppression, the mechanisms of which include defective antigen presentation to T cells and interference with haematopoiesis in the bone marrow (BM). Due to strict species specificity, murine CMV (MCMV) provides a relevant model for the study of CMV modulation of the immune system in vivo in its natural host.

The type I interferons (IFNs) represent a major family of cytokines involved in the early response to MCMV infection. Their anti-viral activity and regulation of NK cell activation and cytotoxicity are of significant interest in the context of MCMV infection, as genetic resistance to MCMV is mediated by the ability of Ly49H+ NK cells to directly recognise and lyse infected cells. Chapter 2 comprises an analysis of acute MCMV infection in the absence of type I IFN activity. These studies were conducted in IFNAR1 and IFNAR2 deficient mice, which lack components of the type I IFN receptor. Data obtained from these studies confirmed the essential requirement for type I IFN in controlling viral titres, promoting expansion of splenic Ly49H+ NK cells, and inducing early activation of NK cell cytotoxicity. In addition, our data depicted an accumulation of infected myeloid cells in the absence of effective NK cell-mediated control. This was paralleled by a significant increase in the level of serum TNF-α and IFN-g, an effect which in some cases has been linked to serious pathological disease. Thus, the data described in this chapter provide an insight into the consequences arising from delayed NK cell responses to MCMV infection in the absence of type I IFN.
Original languageEnglish
QualificationDoctor of Philosophy
Publication statusUnpublished - 2008


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