Project: HIV infection and cholesterol metabolism
Infectious diseases caused by pathogens, such as viruses, are often accompanied by a broad range of co-morbidities. While intracellular pathogens often target one or very few cell types, clinical manifestations of infections are not limited to impairment of the infected organ or tissue, instead they are often associated with profound systemic effects on many organs and tissues that are not infected. Knowing how the effects of infection are “transmitted” to uninfected tissues and systemically is a key to understanding pathogenesis of co-morbidities of viral infections. Any infection triggers both innate and adaptive immune responses and inflammation. However, in addition to this damage caused by ‘overreaction’ of the host to viral infection, many viral infections are associated with specific co-morbidities. In particular, HIV infection is associated with atherosclerosis, dyslipidemia, metabolic syndrome, dementia and impaired haematopoiesis. Importantly, these co-morbidities persist after effective antiretroviral treatment (ART) is initiated and HIV replication is supressed. Tissues involved in pathogenesis of these conditions are often not infected by HIV, and the severity of impairment cannot be fully explained by a mild inflammation characteristic for treated HIV infection. A common element of pathogenesis of many of these co-morbidities is impairment of cholesterol metabolism. Published data from our and other laboratories strongly indicate that HIV infection affects host cholesterol metabolism systemically; these effects may be an underlying mechanism of a number of co-morbidities associated with HIV infection. In this project we will focus on important systemic co-morbidities of HIV infection where cholesterol metabolism is a key element of pathogenesis.
This project will be undertaken at the Baker Herat and Diabetes Institute.
The Sviridov's research is focused on molecular, cellular and clinical aspects of lipid and lipoprotein metabolism in relation to atherosclerosis and cardiovascular disease.