Shilpa Buch

By Ming‐Lei Guo, Palsamy Periyasamy and Shilpa Buch

Despite the dramatic success of combined antiretroviral therapies (cART) in controlling peripheral virus replication, the prevalence of HIV‐1‐associated neurocognitive disorders (HAND) is on a rise as infected individuals continue to live longer. Almost half of the infected individuals on ART develop HAND, out of which at least 30% suffer from a comorbid condition of substance abuse. Involvement of autophagy has been implicated not only in HIV‐1 infection of the CNS but also in CNS cells exposed to drugs such as amphetamine, opiates, and cocaine, contributing in turn, to cellular dysfunction. HIV‐1 is known to interfere with the autophagy pathway, resulting in turn to upregulation of HIV‐1 replication. Specifically, different HIV‐1 proteins such as TAT, gp120, and Nef have been shown to act on various stages of autophagy such as initiation and maturation and to affect overall autophagy levels. Whether or not abused drugs and HIV‐1 can cooperate to dysregulate autophagy, however, remains unclear. This chapter is focused on identifying the molecular mechanism(s) underlying HIV‐1 (proteins) and cocaine, opiate, methamphetamine‐mediated impairment of autophagy. Such effects could underlie the synergistic effects of HIV‐1 and abused drugs in exacerbating symptoms of HAND.

Part of the book: Autophagy in Current Trends in Cellular Physiology and Pathology