Exit Seminar - The brain and HIV-1 infection: inflammation processes in humanized BLT mice and neurological changes
presents a seminar by:
Sponsored by the UBC Department of Microbiology and Immunology.
Abstract: Advances in anti-retroviral therapy (ART), policies, prevention programs and care distribution have led to considerable decrease in the number of AIDS-defining illnesses and related deaths, with an accompanying increase in life expectancy. Concurrently, people living with HIV (PLWH) are faced with novel challenges. For example, age- and HIV-related inflammation contribute to an increased risk of neurocognitive impairment. In fact, approximately 50% of ART-treated individuals experience HIV-associated neurocognitive disorders (HAND), and the prevalence of HAND is increasing. This suggests the need for a better understanding of HAND pathophysiology using an effective animal model. Our research aims to investigate the subclinical and clinical features of HAND using the humanized Bone marrow Liver Thymus (BLT) mouse model. Here, we report that infiltrating macrophages in the brains of HIV-1 infected BLT mice colocalize with the expression of HIV-1 p24 protein. Brain infection also associated with decreased expression of mouse occludin and claudin-5, both markers of blood-brain barrier permeability. Similarly, infected mice had significantly reduced performance in the accelerating rotarod test and poorer performance in the open field test when compared to uninfected mice. This indicates motor deficiency and loss of coordination, a characteristic symptom of HAND in PWLH. While mouse models have previously been used to evaluate HAND, none have characterised the clinical manifestations of HAND in BLT mice, which have mucosal reconstitution and therefore display biologically relevant compartments for the study of HIV-1 pathogenesis. Our results thus far underscore the BLT mouse model of infection as a tool for the characterization of HIV-1 neuro-inflammation and exploration of HAND targets. Ultimately, the elucidation of mechanisms of neuroinflammation during HIV-1 infection will inform the development of novel approaches to bridge the gap between the poor brain penetrance of current ART and the increasing prevalence of HAND.
This is a hybrid seminar which you can attend in person in LSC3 (Life Sciences Institute, UBC Vancouver Campus) or on Zoom. If you are joining on zoom, please use the meeting ID and passcode below:
Join a Meeting: https://ubc.zoom.us/
Meeting ID: 99243 646368