Vinay K. Pathak
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View article: Elucidating the mechanism by which HIV-1 nucleocapsid mutations confer resistance to integrase strand transfer inhibitors
Elucidating the mechanism by which HIV-1 nucleocapsid mutations confer resistance to integrase strand transfer inhibitors Open
Persons with HIV (PWH) receiving integrase (IN) strand transfer inhibitors (INSTIs) have been reported to experience virologic failure (VF) in the absence of resistance mutations in IN. We previously reported that mutations in the viral nu…
View article: The central pore of HIV-1 capsomers promotes sustained stability of the viral capsid
The central pore of HIV-1 capsomers promotes sustained stability of the viral capsid Open
The HIV-1 capsid, which orchestrates several key post-entry events to facilitate infection in target cells, is composed of hexamers and pentamers (capsomers) of the capsid (CA) protein arranged in a closed, conical structure known as the c…
View article: Elucidating the Mechanism by Which HIV-1 Nucleocapsid Mutations Confer Resistance to Integrase Strand Transfer Inhibitors
Elucidating the Mechanism by Which HIV-1 Nucleocapsid Mutations Confer Resistance to Integrase Strand Transfer Inhibitors Open
Persons with HIV (PWH) receiving integrase (IN) strand transfer inhibitors (INSTIs) have been reported to experience virologic failure (VF) in the absence of resistance mutations in IN. We previously reported that mutations in the viral nu…
View article: How to recover from a bad start: adaptation of HIV-1 transcription start site mutants during serial passaging in culture
How to recover from a bad start: adaptation of HIV-1 transcription start site mutants during serial passaging in culture Open
HIV-1 uses neighboring sequences as transcription start sites and generates multiple unspliced transcripts, including two major transcripts with three guanosines (3G) or one guanosine (1G) at the 5′ end. Although only differing by 2-nt, 3G…
View article: Lenacapavir-induced Lattice Hyperstabilization is Central to HIV-1 Capsid Failure at the Nuclear Pore Complex and in the Cytoplasm
Lenacapavir-induced Lattice Hyperstabilization is Central to HIV-1 Capsid Failure at the Nuclear Pore Complex and in the Cytoplasm Open
Lenacapavir (LEN) is the first HIV-1 capsid inhibitor approved for clinical use. It inhibits multiple steps of the viral life cycle; however, the molecular details of the effect of LEN on capsid structure and the mechanistic steps of the i…
View article: Elements in the 5′ Untranslated Region of Viral RNA Important for HIV Gag Recognition and Cross-Packaging
Elements in the 5′ Untranslated Region of Viral RNA Important for HIV Gag Recognition and Cross-Packaging Open
During retrovirus assembly, Gag packages unspliced viral RNA as the virion genome. Genome packaging is usually specific with occasional exceptions of cross-packaging RNA from distantly related retroviruses. For example, HIV-1 Gag can effic…
View article: Lenacapavir disrupts HIV-1 core integrity while stabilizing the capsid lattice
Lenacapavir disrupts HIV-1 core integrity while stabilizing the capsid lattice Open
Lenacapavir (GS-6207; LEN) is a potent HIV-1 capsid inhibitor approved for treating multidrug-resistant infection. LEN binds to a hydrophobic pocket between neighboring capsid (CA) proteins in hexamers and stabilizes the capsid lattice, bu…
View article: HIV-1 transcription start sites usage and its impact on unspliced RNA functions in people living with HIV
HIV-1 transcription start sites usage and its impact on unspliced RNA functions in people living with HIV Open
HIV-1 unspliced RNA serves two distinct functions during viral replication: it is packaged into particles as the viral genome, and it is translated to generate Gag/Gag-Pol polyproteins required for virus assembly. Recent studies have demon…
View article: HIV-1 uncoating requires long double-stranded reverse transcription products
HIV-1 uncoating requires long double-stranded reverse transcription products Open
HIV-1 cores, which contain the viral genome and replication machinery, must disassemble (uncoat) during viral replication. However, the viral and host factors that trigger uncoating remain unidentified. Recent studies show that infectious …
View article: Potent dual block to HIV-1 infection using lentiviral vectors expressing fusion inhibitor peptide mC46- and Vif-resistant APOBEC3G
Potent dual block to HIV-1 infection using lentiviral vectors expressing fusion inhibitor peptide mC46- and Vif-resistant APOBEC3G Open
Gene therapy strategies that effectively inhibit HIV-1 replication are needed to reduce the requirement for lifelong antiviral therapy and potentially achieve a functional cure. We previously designed self-activating lentiviral vectors tha…
View article: HIV-1 usurps transcription start site heterogeneity of host RNA polymerase II to maximize replication fitness
HIV-1 usurps transcription start site heterogeneity of host RNA polymerase II to maximize replication fitness Open
HIV-1 relies on host RNA polymeraseII (Pol II) to transcribe its genome and uses multiple transcription start sites (TSS), including three consecutive guanosines located near the U3-R junction, to generate transcripts containing three, two…
View article: The capsid lattice engages a bipartite NUP153 motif to mediate nuclear entry of HIV-1 cores
The capsid lattice engages a bipartite NUP153 motif to mediate nuclear entry of HIV-1 cores Open
Increasing evidence has suggested that the HIV-1 capsid enters the nucleus in a largely assembled, intact form. However, not much is known about how the cone-shaped capsid interacts with the nucleoporins (NUPs) in the nuclear pore for cros…
View article: Adaptation of HIV-1/HIV-2 Chimeras with Defects in Genome Packaging and Viral Replication
Adaptation of HIV-1/HIV-2 Chimeras with Defects in Genome Packaging and Viral Replication Open
Novel retroviruses can emerge from recombination between distantly related retroviruses. Most notably, HIV-1 originated from zoonotic transmission of a novel recombinant (SIV cpz ) into humans.
View article: Transcription Start Site Heterogeneity and Preferential Packaging of Specific Full-Length RNA Species Are Conserved Features of Primate Lentiviruses
Transcription Start Site Heterogeneity and Preferential Packaging of Specific Full-Length RNA Species Are Conserved Features of Primate Lentiviruses Open
Unspliced HIV-1 RNA serves two important roles during viral replication: as the virion genome and as the template for translation of Gag/Gag-Pol. Previous studies of two HIV-1 molecular clones have concluded that the TSS usage affects unsp…
View article: Intranuclear Positions of HIV-1 Proviruses Are Dynamic and Do Not Correlate with Transcriptional Activity
Intranuclear Positions of HIV-1 Proviruses Are Dynamic and Do Not Correlate with Transcriptional Activity Open
HIV-1 integrates its genomic DNA into the chromosomes of the infected cell, but how it selects the site of integration and the impact of their location in the 3-dimensional nuclear space is not well understood. Here, we examined the nuclea…
View article: Plasma Membrane Anchoring and Gag:Gag Multimerization on Viral RNA Are Critical Properties of HIV-1 Gag Required To Mediate Efficient Genome Packaging
Plasma Membrane Anchoring and Gag:Gag Multimerization on Viral RNA Are Critical Properties of HIV-1 Gag Required To Mediate Efficient Genome Packaging Open
To generate infectious virions, HIV-1 must package its full-length RNA as the genome during particle assembly. HIV-1 Gag:RNA interactions mediate genome packaging, but the mechanism remains unclear.
View article: Selective packaging of HIV-1 RNA genome is guided by the stability of 5′ untranslated region polyA stem
Selective packaging of HIV-1 RNA genome is guided by the stability of 5′ untranslated region polyA stem Open
Significance HIV-1 must select and package its RNA genome from an abundant pool of cellular RNAs. To understand this essential replication step, we studied two nearly identical HIV-1 RNAs that are differentially encapsidated. HIV-1 RNA wit…
View article: HIV-1 cores retain their integrity until minutes before uncoating in the nucleus
HIV-1 cores retain their integrity until minutes before uncoating in the nucleus Open
Significance Here, we used a fluorescent protein that is free in solution and is trapped in nuclear HIV-1 capsids to demonstrate that the capsids retain integrity and prevent mixing of macromolecules within the viral core and the cellular …
View article: Development of a Cell-Based Luciferase Complementation Assay for Identification of SARS-CoV-2 3CLpro Inhibitors
Development of a Cell-Based Luciferase Complementation Assay for Identification of SARS-CoV-2 3CLpro Inhibitors Open
The 3C-like protease (3CLpro) of SARS-CoV-2 is considered an excellent target for COVID-19 antiviral drug development because it is essential for viral replication and has a cleavage specificity distinct from human proteases. However, drug…
View article: Impact of Nuclear Export Pathway on Cytoplasmic HIV-1 RNA Transport Mechanism and Distribution
Impact of Nuclear Export Pathway on Cytoplasmic HIV-1 RNA Transport Mechanism and Distribution Open
The unspliced HIV-1 full-length RNA (HIV-1 RNA) is packaged into virions as the genome and is translated to generate viral structural proteins and enzymes. To serve these functions, HIV-1 RNA must be exported from the nucleus to the cytopl…
View article: Isoform-specific characterization implicates alternative splicing in<i>APOBEC3B</i>as a mechanism restricting APOBEC-mediated mutagenesis
Isoform-specific characterization implicates alternative splicing in<i>APOBEC3B</i>as a mechanism restricting APOBEC-mediated mutagenesis Open
APOBEC3A (A3A) and APOBEC3B (A3B) enzymes drive APOBEC-mediated mutagenesis, but the understanding of the regulation of their mutagenic activity remains limited. Here, we showed that mutagenic and non-mutagenic A3A and A3B enzymes are prod…
View article: Unpaired Guanosines in the 5′ Untranslated Region of HIV-1 RNA Act Synergistically To Mediate Genome Packaging
Unpaired Guanosines in the 5′ Untranslated Region of HIV-1 RNA Act Synergistically To Mediate Genome Packaging Open
HIV-1 must package its RNA genome during virus assembly to generate infectious viruses. To better understand how HIV-1 packages its RNA genome, we examined the roles of RNA elements identified as binding sites for NC, a Gag-derived RNA-bin…
View article: Effect of P‐body component Mov10 on HCV virus production and infectivity
Effect of P‐body component Mov10 on HCV virus production and infectivity Open
Mov10 is a processing body (P‐body) protein and an interferon‐stimulated gene that can affect replication of retroviruses, hepatitis B virus, and hepatitis C virus (HCV). The mechanism of HCV inhibition by Mov10 is unknown. Here, we invest…
View article: Structural Insights into APOBEC3-Mediated Lentiviral Restriction
Structural Insights into APOBEC3-Mediated Lentiviral Restriction Open
Mammals have developed clever adaptive and innate immune defense mechanisms to protect against invading bacterial and viral pathogens. Human innate immunity is continuously evolving to expand the repertoire of restriction factors and one s…
View article: Visualizing the translation and packaging of HIV-1 full-length RNA
Visualizing the translation and packaging of HIV-1 full-length RNA Open
Significance The major viral components of HIV-1 virions are full-length RNA (HIV-1 RNA) and its translation products. Packaged HIV-1 RNA carries viral genetic information, and its translation products Gag and Gag-Pol constitute the virus …