CO-MORBIDITY IN RELATION TO HIV/AIDS (COBRA)
Supervisors: Julien Villaudy, Ben Berkhout & Andries Kalsbeek
A number of features of the metabolic syndrome, such as insulin resistance, hypertriglyceridaemia and abnormal distribution of adipose tissue, are a prominent component of age-associated non-communicable co-morbidities (AANCC), frequently observed in HIV-infected subjects. In order to study the respective roles of HIV infection and combination antiretroviral therapy (cART) in the origin of these features of the metabolic syndrome, we will investigate the development of insulin resistance and adiposity in the “Human Immune System” (HIS) mouse model.
The hypothalamus has long been appreciated to be fundamental in the control and coordination of the peripheral energy metabolism. More recently, the control over the autonomic nervous system emanating from the hypothalamus has been increasingly recognized as a powerful additional modulator of peripheral tissues, more generally. This integration of neural inputs to the endocrine-based pathogenesis of diseases such as diabetes, obesity and osteoporosis also offers the interesting possibility that HIV-/cART-induced neuronal damage is at the origin of the metabolic components of the AANCC.
Experiments will be performed with the use of the NOD/scid-IL-2Rgc-/- “Human Immune System” mouse model (NSG-HIS), generated by engrafting purified hHPCs in sublethally irradiated, newborn NSG mice. NSG-HIS mice will be analyzed prior to and after HIV-1 infection, in the absence and presence of cART for up to 24 weeks, allowing us to study long-term changes as well as ageing in the animals.
This project is a joined effort at the AMC of the HIS mouse platform and the Departments of Medical Microbiology (Laboratory for Experimental Virology), Experimental Immunology, and Endocrinology & Metabolism.