Viruses are major contributors to global health crises. Many of the disease pandemics the world has experienced were caused by viruses from smallpox to Spanish flu, Ebola (Public health emergency of international concern), SARS, West Nile, Zika and currently SARS-CoV-2 the aetiology of COVID19. At the centre of the virus-host interaction is a unique group of cells called the antigen presenting cells (APC). APC play a significant role in immune response, as the receptionist, they are the first cells to detect pathogen invasion and present the antigen to the cells of the adaptive immune system for activation and clearance of the pathogen. This unique function as the receptionist and coordinator of signals makes them critical players in directing the outcome of an immune response. Therefore, they are critical in understanding the dynamics of viral infection, why certain viruses are cleared while others persist; the study of virus interaction with APC is a vital area to start. This thesis investigates the role of APC in virus infection, persistence and immunopathology using the LCMV model. The LCMV model is a well-established model system for studying the immune system and its interaction with pathogen. It has contributed to some fundamental discoveries in the field of immunology and virology; for example, understanding the role of the major histocompatibility complex. Though the LCMV model has been a critical player in the field of immunology and virology, most of the data from the model are from bulk analyses and made use of available resources at the time. With the advent of high throughput technologies such as the single cell RNA sequencing, this thesis revisits the LCMV-APC (DC and macrophage/monocytes) interaction at the in vitro, in vivo and single-cell level. The findings from the in vitro study confirmed the heterogeneity of in vitro bone marrow derived cells as opposed to the previous view that they were mainly DC whilst macrophages are generated only by M-CSF growth factor. This heterogeneity was present after differentiating cells in the presence of all the growth factors commonly used for generating in vitro BM-DC. Moreso, the result confirmed functional differences between the DC (BM-DC) and macrophage (BM-M) subsets. While BM-DC were better at antigen presentation to T cells, BM-M were more efficient cytokine producers. The in vivo study validated the immunosuppressive nature of LCMV in virus persistence. LCMV clone 13 infected all subsets of splenic DC and macrophages and impaired expression of antiviral and inflammatory cytokine genes as well as antigen presentation genes in APC. However, this impairment was temporary and was overridden by secondary stimulation with poly (I:C). Taken together, this thesis has shown the division of labour amongst APC in their interaction with the virus. It also demonstrated the power of single-cell sequencing technology and how it is helping to recognise the dynamic nature of the immune response at the single-cell transcriptome level. With more availability of high-throughput technology, there is a need to revisit some of the previous studies that were based on bulk analyses of the immune response to viruses. Understanding the dynamic nature of immunity and the individual contribution at the cellular level will improve our efficiency and precision in designing intervention measures.