HIV-1 Rev downregulates Tat expression and viral replication via modulation of NAD(P)H:quinine oxidoreductase 1 (NQO1)

Lata, Sneh; Ali, Amjad; Sood, Vikas; Raja, Rameez; Banerjea, Akhil C.

doi:10.1038/ncomms8244

Cited by 46 publications

(58 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The direct interaction between HIV-1 Rev and Tat has been detected by two-hybrid assays, pulldown assays, and coimmunoprecipitation assays (216). The nuclear export signal region of HIV-1 Rev (Fig.…”

Section: Tat-rev Interactionmentioning

confidence: 99%

“…The nuclear export signal region of HIV-1 Rev (Fig. 2) takes part in the proteasomal degradation of cytoplasmic Tat at the posttranslational level, leading to a significant decrease of HIV-1 gene expression (216). The Revmediated downregulation of Tat might be associated with HIV-1 latency, because the decrease of the intracellular level of Tat below a critical threshold potentially marks the rise of HIV-1 latency (216).…”

Section: Tat-rev Interactionmentioning

confidence: 99%

“…2) takes part in the proteasomal degradation of cytoplasmic Tat at the posttranslational level, leading to a significant decrease of HIV-1 gene expression (216). The Revmediated downregulation of Tat might be associated with HIV-1 latency, because the decrease of the intracellular level of Tat below a critical threshold potentially marks the rise of HIV-1 latency (216). Moreover, the regulatory proteins Rev and Tat shuttle between the nucleus and the cytoplasm to interact with various cellular factors (4,216).…”

Section: Tat-rev Interactionmentioning

confidence: 99%

“…The Revmediated downregulation of Tat might be associated with HIV-1 latency, because the decrease of the intracellular level of Tat below a critical threshold potentially marks the rise of HIV-1 latency (216). Moreover, the regulatory proteins Rev and Tat shuttle between the nucleus and the cytoplasm to interact with various cellular factors (4,216). HIV-1 Rev and Tat expressed via viral preintegration transcription (Fig.…”

Section: Tat-rev Interactionmentioning

confidence: 99%

“…(iv) At the late stage of viral transcription, the proteasomal degradation of Tat is induced by viral nucleocapsid (228). Moreover, Rev induces Tat degradation by downregulating the expression level of the cellular protein NQO1 (216). Question marks indicate unclear interaction domains.…”

Section: Tat-rev Interactionmentioning

confidence: 99%

See 4 more Smart Citations

HIV Genome-Wide Protein Associations: a Review of 30 Years of Research

Clercq

2016

Microbiol Mol Biol Rev

View full text Add to dashboard Cite

SUMMARYThe HIV genome encodes a small number of viral proteins (i.e., 16), invariably establishing cooperative associations among HIV proteins and between HIV and host proteins, to invade host cells and hijack their internal machineries. As a known example, the HIV envelope glycoprotein GP120 is closely associated with GP41 for viral entry. From a genome-wide perspective, a hypothesis can be worked out to determine whether 16 HIV proteins could develop 120 possible pairwise associations either by physical interactions or by functional associations mediated via HIV or host molecules. Here, we present the first systematic review of experimental evidence on HIV genome-wide protein associations using a large body of publications accumulated over the past 3 decades. Of 120 possible pairwise associations between 16 HIV proteins, at least 34 physical interactions and 17 functional associations have been identified. To achieve efficient viral replication and infection, HIV protein associations play essential roles (e.g., cleavage, inhibition, and activation) during the HIV life cycle. In either a dispensable or an indispensable manner, each HIV protein collaborates with another viral protein to accomplish specific activities that precisely take place at the proper stages of the HIV life cycle. In addition, HIV genome-wide protein associations have an impact on anti-HIV inhibitors due to the extensive cross talk between drug-inhibited proteins and other HIV proteins. Overall, this study presents for the first time a comprehensive overview of HIV genome-wide protein associations, highlighting meticulous collaborations between all viral proteins during the HIV life cycle.

show abstract

Section: Tat-rev Interactionmentioning

confidence: 99%

Section: Tat-rev Interactionmentioning

confidence: 99%

Section: Tat-rev Interactionmentioning

confidence: 99%

Section: Tat-rev Interactionmentioning

confidence: 99%

Section: Tat-rev Interactionmentioning

confidence: 99%

See 3 more Smart Citations

HIV Genome-Wide Protein Associations: a Review of 30 Years of Research

Clercq

2016

Microbiol Mol Biol Rev

View full text Add to dashboard Cite

show abstract

Novel Dioxolan Derivatives of Indole as HIV‐1 Integrase Strand Transfer Inhibitors Active Against RAL Resistant Mutant Virus

Singh

Yadav²,

Urvashi³

et al. 2016

ChemistrySelect

View full text Add to dashboard Cite

Drugs have been discovered to treat HIV-1 but mutation in virus causing resistance to drug, necessitates a continuous development of novel molecules. We have developed new chemical constructs that target HIV-1 integrase (HIV-IN) and it's mutant. We have evaluated 22 dioxolan and malonyl derivatives of indole. It was observed that C-3 substituted dioxolan derivatives 13 c and 13 o exhibited outstanding strand transfer inhibitory activity with IC 50 at 5.7 and 0.2 mM respectively. The therapeutic index of 13 o was comparable to raltegravir (RAL). Compounds 13 c and 13 o not only showed excellent antiviral activity (EC 50 ) in wild type, a moderate activity was also observed against mutant IN i. e. G140S (4.7 and 0.2 mM) and Y143R (5.0 and 0.37 mM) respectively. The computational study suggested that these inhibitors bind centrally at the active site of integrase making a close contact with the residues in or around the active site of wild type and mutant proteins. Thus the newly synthesized dioxolan derivatives opened the possibility for development of more effective IN inhibitors exploiting the strategy mentioned in our paper.

show abstract