The Mechanism Of The Suppression Of HIV-1 Replication By The Immune Regulator ABIN1

Aquired immune deficiency syndrom(AIDS)is a widespread epidemic with the etiologic agent of Human immunodeficiency virus(HIV).HIV belongs to retrovirus and includs two subtypes,HIV-1 and HIV-2,while HIV-1 is the major one that causes the disease.As a retrovirus,the genome of HIV-1 integrates into the chromosome of the host cell after entering the cell.Depending on the intracellular environment,it can initiate productive replication cycle,or become latent to be reactived at the preferred condition and cause pathologic damage.HIV-1 transmisses mainly through the blood transfution,body fluids,intercourse and vertical transmission between the mater and fetus.Currently,HIV-1 infection is incurable,making it the hotspot of biological research.A20-Binding Inhibitor of NF-?B activation(ABIN1),an important immune regulator,was previously shown to be involved in HIV-1 replication.However,the reported studies done with overexpressed ABIN1 provided controversial results.Here we identified ABIN1 as a suppressor of HIV-1 transcription since transient knockdown of ABIN1 led to increased HIV-1 replication both in Jurkat T cell line and in primary human CD4+ T lymphocytes.Depletion of ABIN1 specifically enhanced the HIV-1 transcription from the integrated genome during viral life cycle,but not the earlier steps such as reverse transcription or integration.Immunoprecipitation assays revealed that ABIN1 specifically inhibits the proto-oncogene HDM2 catalyzed K63-linked polyubiquitination of Tat at Lys71,which is critical for the transactivation activity of Tat.The ubiquitin chain binding activity of ABIN1 carried by UBAN domain turned out to be essential for the inhibitory role of ABIN1.The results of immunofluorescence localization experiments suggested that ABIN1 may obstruct Tat ubiquitination by redistributing some of HDM2 from the nucleus to the cytoplasm.Our findings have revealed ABIN1 as intrinsic suppressor of HIV-1 mRNA transcription by regulating the ubiquitination of Tat.