Figure 6.

Proposed components of learning impairment caused by astrocytic Nef expression. Nef protein is produced in astrocytes (1) resulting in induction of CCL2 (2). The secreted CCL2 serves as a powerful attractant to peripheral monocytes that migrate to the brain (2a) and differentiate to macrophages expressing CD163 (2b). These macrophages contribute to the local inflammatory environment resulting in the loss of neurons (3). Nef released from astrocytes (4) may compromise the blood brain barrier (4a) and cause direct neurotoxicity (4b). Finally, Nef production in astrocytes can promote release of proinflammatory molecules (5) further contributing to the neurotoxic environment. The loss of neuron numbers and function results in learning impairment. Solid lines indicate findings from this study; dashed lines are based on other published data.