Targeting the Integrated Stress Response Kinase GCN2 to Modulate Retroviral Integration
Molecules, 2021 Multiple viral targets are now available in the clinic to fight HIV infection. Even if this targeted therapy is highly effective at suppressing viral replication, caregivers are facing growing therapeutic failures in patients due to resistance, with or ...
Chloé Torres +5 more
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Three main mutational pathways in HIV-2 lead to high-level raltegravir and elvitegravir resistance: implications for emerging HIV-2 treatment regimens. [PDF]
PLoS ONE, 2012 Human immunodeficiency virus type 2 (HIV-2) is intrinsically resistant to non-nucleoside reverse transcriptase inhibitors and exhibits reduced susceptibility to several of the protease inhibitors used for antiretroviral therapy of HIV-1. Thus, there is a
Robert A Smith +10 more
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Dialysis purification of integrase-DNA complexes provides high-resolution atomic force microscopy images: dimeric recombinant HIV-1 integrase binding and specific looping on DNA. [PDF]
PLoS ONE, 2013 It remains difficult to obtain high-resolution atomic force microscopy images of HIV-1 integrase bound to DNA in a dimeric or tetrameric fashion. We therefore constructed specific target DNAs to assess HIV-1 integrase binding and purified the complex by ...
Tatsuaki Tsuruyama +5 more
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Modeling the HIV-1 Intasome: A Prototype View of the Target of Integrase Inhibitors
Viruses, 2010 The HIV-1 integrase enzyme is essential for integrating the viral DNA into the host chromosome. Infection is aborted in the absence of integration, making integrase an attractive antiviral target. Recently approved inhibitors of integrase bind tightly to
Robert Craigie, Zhiqi Yin
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Comparative biochemical analysis of HIV-1 subtype B and C integrase enzymes
Retrovirology, 2009 Background Integrase inhibitors are currently being incorporated into highly active antiretroviral therapy (HAART). Due to high HIV variability, integrase inhibitor efficacy must be evaluated against a range of integrase enzymes from different subtypes ...
Kuhl Björn D +7 more
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Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. [PDF]
PLoS ONE, 2013 Signature HIV-1 integrase mutations associated with clinical raltegravir resistance involve 1 of 3 primary genetic pathways, Y143C/R, Q148H/K/R and N155H, the latter 2 of which confer cross-resistance to elvitegravir. In accord with clinical findings, in
Felix DeAnda +6 more
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HIV-1 integrase modulates the interaction of the HIV-1 cellular cofactor LEDGF/p75 with chromatin
Retrovirology, 2011 Background Chromatin binding plays a central role in the molecular mechanism of LEDGF/p75 in HIV-1 DNA integration. Conflicting results have been reported in regards to the relevance of the LEDGF/p75 chromatin binding element PWWP domain in its HIV-1 ...
Garcia-Rivera Jose A +5 more
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mBio, 2020 Integration of the proviral DNA intermediate into the host cell genome normally represents an essential step in the retroviral life cycle. While the reason(s) for this requirement remains unclear, it is known that unintegrated proviral DNA is ...
Ishak D. Irwan +4 more
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Biochemical and virological analysis of the 18-residue C-terminal tail of HIV-1 integrase
Retrovirology, 2009 Background The 18 residue tail abutting the SH3 fold that comprises the heart of the C-terminal domain is the only part of HIV-1 integrase yet to be visualized by structural biology.
Di Nunzio Francesca +6 more
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Virus evolution reveals an exclusive role for LEDGF/p75 in chromosomal tethering of HIV. [PDF]
PLoS Pathogens, 2007 Retroviruses by definition insert their viral genome into the host cell chromosome. Although the key player of retroviral integration is viral integrase, a role for cellular cofactors has been proposed.
Anneleen Hombrouck +10 more
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