Description:

Title: "HIV Sanctuary Sites: The Brain/Peripheral Organ Connection

Lena Al-Harthi, PhD - Rush University

Host: Mojgan Naghavi, PhD

Description:

Twenty-five years ago, an HIV diagnosis meant a death sentence within 4-6 years. Thankfully, with advances in HV treatment, HIV has become a chronic disease, albeit with considerable co-morbid complications. Nonetheless, scientific efforts are focused on an HIV cure (e.g. eliminating the virus from the body). Those efforts have largely focused on the role of resting memory T cells. Yet, other sanctuary sites for HIV persist that will be a challenge to HIV cure initiatives. HIV enters the brain during acute HIV infection, yet there is an underappreciation for the role of the brain as a reservoir for HIV, largely because it is difficult to probe active virus replication in the brain and also to address how this virus may re-seed the periphery. In this presentation, I will share our body of work regarding the role of the brain, and particularly astrocytes, as an HIV reservoir. Specifically, I will address HIV infection of astrocytes, mechanisms that restrict productive infection, pathways that overcome this restriction, evidence for HIV latency in astrocytes, and HIV dissemination (egress) from the brain (infected astrocytes) to peripheral organs. Further, HIV and its inflammatory sequelae lead to HIV-Associated Neurocognitive Disorders (HAND), I will discuss the mechanisms driving HAND as they relate to dysregulation in astrocyte function and a novel biomarker for HAND. Our collective studies point to brain as a reservoir for HIV, which cannot be viewed as a separate HIV compartment but rather as a contributing source of HIV dissemination into other tissues and highlight the impact of HIV/inflammatory mediators in disrupting astrocytes function contributing to HAND.

r. Al-Harthi’s research is focused on defining mechanism(s) driving HIV neurocognitive disorders (HAND) and HIV latency in the central nervous system. Specifically, she studies the role of astrocytes in HAND and HIV latency/persistence. To date, her body of work has demonstrated that HIV replication in astrocytes is restricted through robust expression of b-catenin signaling, which blocks HIV transcription. Yet, this restriction is overcome by inflammatory mediators allowing for bursts of productive HIV replication and persistence of HIV in astrocytes. Disruption of b-catenin in astrocytes in turn dysregulates astrocyte function leading to neuronal injury. More recently, she developed an innovative xenotransplantation model of human astrocytes into humanized mice to demonstrate that HIV in astrocytes can re-seed peripheral organs contributing to dissemination of HIV throughout the body.