HIV-1 Tat Increases BAG3 Via NF-?B Signaling To Induce Autophagy During HIV-associated Neurocognitive Disorder

In recent years,the incidence of human immunodeficiency virus(HIV)associated neurocognitive disorders(HAND)has increased.We have previously demonstrated that HIV-1 transactivator of transcription Tat(HIV-1 Tat)could upregulate AEG-1 to inhibit EAAT-2 expression in astrocyte,which might contribute to the development of HAND.Recent studies have shown that,in vitro,HIV-1 Tat induced autophagy in neuron.Meanwhile,the dysregulation of autophagy is associated with the pathogenesis of HAND.In addition,Bcl-2-associated athanogene 3(BAG3)has been reported to regulate autophagy in different cell types.We attempt to explore whether BAG3 is involved in the HIV-1 Tat-induced autophagy process during HAND.Interestingly,we show that BAG3 is significantly increased in astrocyte of frontal cortex with simian immunodeficiency virus-human immunodeficiency virus chimeric virus(SHIV)-infected macaques.We further reveal that HIV-1 Tat upregulates BAG3 in a NF-kB-dependent manner to induce autophagy in U87,a human primary glioblastoma cell line.More importantly,both directly knockdown of BAG3 and indirectly knockdown of BAG3 by NF-KB inhibitor reverse HIV-1 Tat-induced autophagy.Collectively,these results indicate that HIV-1 Tat upregulates BAG3 via the NF-KB signaling pathway and then induces autophagy in astrocytes,which may provide a new possible insight for HAND therapy.