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Table 4 Roles of autophagy in HIV-1 infection, pathogenesis, and treatment

From: Dual role of autophagy in HIV-1 replication and pathogenesis

Topic Observations References
HIV-1replication In HeLa cells, autophagy-associated genes are necessary for HIV-1 replication. [42]
In CD4+ T cells, HIV-1 inhibits autophagy as evidenced by decreased autophagosome numbers and reduced levels of Beclin 1 and LC3 II. [44]
HIV-1pathogenesis In macrophages, early nondegradative stages of autophagy promote HIV-1 replication. HIV-1 Gag interacts with LC3 to elevate these stages. The late proteolytic stages of autophagy inhibit HIV-1 replication. Nef interacts with Beclin 1 to inhibit these stages [44, 45]
In bystander T cells, HIV-1 Env induces autophagy and the accumulation of Beclin1 in uninfected CD4+ T cells. This event leads to apoptosis. [46, 47]
Bystander macrophages do not undergo Env-mediated autophagy. HIV-1 inhibits autophagy in bystander macrophage/monocytic cells through an Akt-dependent pathway. [57]
In dendritic cells, HIV-1 capture down-regulates autophagy and immunoamphisomes in monocyte-derived dendritic cells, impairing innate and adaptive immune responses. Plasmacytoid dendritic cells produce IFN-α in response to infectious or noninfectious HIV-1 through autophagy-dependent TLR7 signaling. This response could promote chronic immune activation. [41, 76]
Neurotoxicity. The dysregulation of autophagy is a feature of neuroAIDS. The brains of persons with HIV-1 encephalitis exhibit increased levels of autophagic proteins and autophagosomes. [88, 89]
Treatment * Antiretroviral therapy. HIV-1 protease inhibitors induce autophagy in cancer cells. Clinical concentrations of EFV induce autophagy and, in particular, mitophagy in hepatic cells. ddI treatment restores neuronal LC3 expression in the brains of FIV-infected animals. [90, 91]
  Vitamin D. It has been observed that HIV-infected individuals have reduced levels of the hormonally active form of vitamin D and that this compound has autophagy-dependent anti-HIV-1 effects on macrophages. [36]
  1. * Abbreviations: efavirenz, EFV; feline immunodeficiency virus, FIV; didanosine, ddI.