The host response to virus infection: Studies using the lactate dehydrogenase-elevating virus.

摘要

This research was designed to better understand virus-host interactions. Using a murine model of chronic virus infection, the lactate dehydrogenase-elevating virus (LDV), key elements of the virus-host interaction during acute and chronic virus infections were determined.; For this dissertation research, mice and mouse cells were exposed to virus infections, and experiments were carried out to determine animal and cell responses to virus infection over time. A mouse model of virus-induced paralysis was also studied, to help clarify the relationship of host immune and cellular responses to disease.; The present research has touched on areas which are potentially shared mechanisms among various viruses or virus-related pathologies including: (1) the formation of immune complexes carrying cytokine antigens as a potential mechanism of immunopathology, (2) the transport of virus-infected immune cells in the umbilical cord as a mechanism for fetal delivery of various viruses, and (3) the induction of apoptotic pathways as viral and pathogenic mechanisms.; To study virus mechanisms, several major hypotheses were formulated and tested for this dissertation research. The first hypothesis was that the umbilical cord is a site of maternal-fetal cell traffic, including LDV-infected macrophages. The second hypothesis was that LDV-induced hydrophobic immune complexes bind at specific tissue sites, and that one component of the complexes is TGF-beta. The third hypothesis addressed apoptosis as a mechanism of pathogenesis upon infection with LDV.; The results of this dissertation show that the umbilical cord is a site of active virus infection, contains virus-infected macrophages, and is responsive to maternal antibodies. The results also characterize circulating hydrophobic IgG-containing immune complexes, indicating one non-IgG component to be the cytokine transforming growth factor-beta (TGF-beta). The results also show the role LDV plays in the induction of apoptosis, and the relationship of LDV-induced apoptosis to neuroparalytic disease, as a likely disease mechanism.; Combined, these results help clarify viral mechanisms related to persistence, transmission and pathogenesis. The results of this work have implications for preventative strategies, including vaccine development and immune-modulating therapies, to better manage the effects of the immune response to virus infections.