A new way to reveal how HIV affects cognitive function in the brain!

At present, antiretroviral therapy (Art) is widely used in human immunodeficiency virus infection, Even so, more than 50% of HIV patients still show amnesia, confusion, behavior changes and movement defects, that is, HIV associated neurocognitive disorders (hand). However, due to the unclear mechanism of hand and the lack of representative models, targeted treatment can not be achieved.recently, researchers from Penn Dental College, pelleman medical school and children's Hospital of Philadelphia established a model based on human induced pluripotent stem cell (hiPSC), and found that HIV infection can enhance the eIF2 signal of microglia, astrocytes and neurons.the study was published in the journal stem cell reports.doi: 10.1016/j.stemcr.2020.02.010 it is generally believed that neurons are not directly exposed to HIV, but are damaged during infection; astrocytes send proinflammatory factors to synapses and cause damage; microglia responsible for maintaining a healthy environment will expand and cause inflammation during HIV infection.the researchers independently differentiated hipscs into three types: forebrain like excitatory neurons, astrocytes and microglia, and then mixed them together to explore how HIV infection and art affect cells.the three cell differentiation processes were combined to form tri culture (± HIV infection and Art). Single cell RNA sequence analysis of three cultures of microglia with HIV infection showed that eIF2 signal existed in three cell types, and inflammatory signal was found in microglia.after treatment with EFZ (efavirenz) - antiretroviral compounds, these characteristics were greatly solved, and RhoGDI and CD40 signals in HIV infected microglia were increased, which was related to the continuous increase of transforming growth factor α produced by microglia.HIV infected hiPSC In the tri culture model, art treatment is still accompanied by neuroinflammation and eIF2 signal. In summary, the researchers described three culture methods of microglia, astrocytes and neurons derived from hiPSC, and found that HIV infection can increase eIF2 signal of all three cell types, while EFZ alone can generate inflammatory signal through RNA expression. In addition, infected microglia are also involved The cytoplasmic cells can increase the inflammatory response and decrease the phagocytosis of synapses.in the future, it is hoped that more scientists can explore other aspects of HIV's impact on the brain, such as how HIV passes through the blood-brain barrier.end References: [1] a new way to study HIV's impact on the brain [2] neuroimaging and eIF2 signaling persist destroy antiretroviral treatment in an hiPSC tri culture model of HIV infection