title: HIV-1 Rev downregulates Tat expression and viral replication via modulation of NAD(P)H:quinine oxidoreductase 1 (NQO1).
abstract: HIV-1 gene expression and replication largely depend on the regulatory proteins Tat and Rev, but it is unclear how the intracellular levels of these viral proteins are regulated after infection. Here we report that HIV-1 Rev causes specific degradation of cytoplasmic Tat, which results in inhibition of HIV-1 replication. The nuclear export signal (NES) region of Rev is crucial for this activity but is not involved in direct interactions with Tat. Rev reduces the levels of ubiquitinated forms of Tat, which have previously been reported to be important for its transcriptional properties. Tat is stabilized in the presence of
  quinine oxidoreductase 1 (NQO1), and potent degradation of Tat is induced by dicoumarol, an NQO1 inhibitor. Furthermore, Rev causes specific reduction in the levels of endogenous NQO1. Thus, we propose that Rev is able to induce degradation of Tat indirectly by downregulating NQO1 levels. Our findings have implications in HIV-1 gene expression and latency.
authors.affiliation: Department of Microbiology, University College of Medical Sciences and Guru Teg Bahadur Hospital, Delhi 110095, India.
authors.forename: Sneh
authors.initials: S
authors.lastname: Lata
authors.affiliation: Laboratory of Virology, National Institute of Immunology, New Delhi 110067, India.
authors.forename: Amjad
authors.initials: A
authors.lastname: Ali
authors.affiliation: 1] Department of Microbiology, University College of Medical Sciences and Guru Teg Bahadur Hospital, Delhi 110095, India [2] Laboratory of Virology, National Institute of Immunology, New Delhi 110067, India.
authors.forename: Vikas
authors.initials: V
authors.lastname: Sood
authors.affiliation: Laboratory of Virology, National Institute of Immunology, New Delhi 110067, India.
authors.forename: Rameez
authors.initials: R
authors.lastname: Raja
authors.affiliation: Laboratory of Virology, National Institute of Immunology, New Delhi 110067, India.
authors.forename: Akhil C
authors.initials: AC
authors.lastname: Banerjea
mesh_terms: D015694:Gene Products, rev / Q000378:metabolism*; D015696:Gene Products, tat / Q000378:metabolism*; D015497:HIV-1 / Q000378:metabolism* / Q000502:physiology; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism*; D049790:Nuclear Export Signals; D059748:Proteolysis; D014779:Virus Replication
chemical_list: D015694:Gene Products, rev; D015696:Gene Products, tat; D049790:Nuclear Export Signals; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human