In my final year at university and a question that I can't seem to answer is "critically evaluate the cause of HIV infection. I have chosen to answer the question with the nef gene and how it causes infectivity and evasion from other immune cells which allows infectivity through downregulation of the CD4 and MHC-1 receptors and I'm stuck at how these aspects cause this to happen. Any input would be greatly appreciated. Thanks
By down regulating cell surface expression of CD4 and Lck, Nef creates a narrow TCR response which likely optimizes HIV-1 viral production and generates a susceptible population of cells to further infect. Nef retargets kinase-active Lck away from the plasma membrane to early and recycling endosomes (RE) as well as the Trans-Golgi network (TGN). RE/TGN associated Lck sub-populations in Nef expressing cells are in the catalytically active conformation and thus signaling competent.[4] While TCR signaling takes place at the plasma membrane (PM), activation of the Ras-GTPase takes place in intracellular compartments including the Golgi apparatus. Nef induced enrichment of active Lck in these compartments results in an increase of localized RAS activity and enhanced activation of Erk kinase and the production of Interleukin-2 (IL-2).
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