Jonathan Rawson
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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: Independent FDA Analyses of Nirmatrelvir/Ritonavir Resistance in the Phase 2/3 Trials EPIC-HR and EPIC-SR
Independent FDA Analyses of Nirmatrelvir/Ritonavir Resistance in the Phase 2/3 Trials EPIC-HR and EPIC-SR Open
Background PAXLOVID consists of nirmatrelvir, an inhibitor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (Mpro), copackaged with ritonavir, a pharmacokinetic enhancer. Nirmatrelvir/ritonavir received emergen…
View article: Evaluation of SARS-CoV-2 RNA Rebound After Nirmatrelvir/Ritonavir Treatment in Randomized, Double-Blind, Placebo-Controlled Trials — United States and International Sites, 2021–2022
Evaluation of SARS-CoV-2 RNA Rebound After Nirmatrelvir/Ritonavir Treatment in Randomized, Double-Blind, Placebo-Controlled Trials — United States and International Sites, 2021–2022 Open
Rebound of SARS-CoV-2 shedding or COVID-19 signs and symptoms has been described after treatment with nirmatrelvir/ritonavir (Paxlovid). The direct association of nirmatrelvir/ritonavir to COVID-19 rebound remains unclear because most repo…
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: Uses and Challenges of Antiviral Polyclonal and Monoclonal Antibody Therapies
Uses and Challenges of Antiviral Polyclonal and Monoclonal Antibody Therapies Open
Viral diseases represent a major public health concerns and ever-present risks for developing into future pandemics. Antiviral antibody therapeutics, either alone or in combination with other therapies, emerged as valuable preventative and…
View article: Uses and Challenges of Antiviral Polyclonal and Monoclonal Antibody Therapies
Uses and Challenges of Antiviral Polyclonal and Monoclonal Antibody Therapies Open
Viral diseases represent a major public health concern and an ever-present risk for developing into a future pandemic. Antiviral antibody therapeutics, either alone or in combination with other therapies, have emerged as valuable preventat…
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: 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: 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: 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: HIV-1 uncoats in the nucleus near sites of integration
HIV-1 uncoats in the nucleus near sites of integration Open
Significance For several decades, retroviral core uncoating has been thought to occur in the cytoplasm in coordination with reverse transcription, and while some recent studies have concluded that HIV-1 uncoating occurs at the nuclear enve…
View article: Recombination is required for efficient HIV-1 replication and the maintenance of viral genome integrity
Recombination is required for efficient HIV-1 replication and the maintenance of viral genome integrity Open
Retroviruses package two complete RNA genomes into a viral particle but generate only one provirus after each infection. This pseudodiploid replication strategy facilitates frequent recombination, which occurs during DNA synthesis when rev…
View article: 5-Azacytidine Enhances the Mutagenesis of HIV-1 by Reduction to 5-Aza-2′-Deoxycytidine
5-Azacytidine Enhances the Mutagenesis of HIV-1 by Reduction to 5-Aza-2′-Deoxycytidine Open
5-Azacytidine (5-aza-C) is a ribonucleoside analog that induces the lethal mutagenesis of human immunodeficiency virus type 1 (HIV-1) by causing predominantly G-to-C transversions during reverse transcription. 5-Aza-C could potentially act…
View article: Studies On The Determinants Of HIV Mutagenesis And Strategies For Its Enhancement
Studies On The Determinants Of HIV Mutagenesis And Strategies For Its Enhancement Open
University of Minnesota Ph.D. dissertation. December 2015. Major: Molecular, Cellular, Developmental Biology and Genetics. Advisor: Louis Mansky. 1 computer file (PDF); xii, 374 pages + 5 supplementary files
View article: Lack of Mutational Hot Spots during Decitabine-Mediated HIV-1 Mutagenesis
Lack of Mutational Hot Spots during Decitabine-Mediated HIV-1 Mutagenesis Open
Decitabine has previously been shown to induce lethal mutagenesis of human immunodeficiency virus type 1 (HIV-1). However, the factors that determine the susceptibilities of individual sequence positions in HIV-1 to decitabine have not yet…
View article: Additional file 2: of HIV-1 and HIV-2 exhibit similar mutation frequencies and spectra in the absence of G-to-A hypermutation
Additional file 2: of HIV-1 and HIV-2 exhibit similar mutation frequencies and spectra in the absence of G-to-A hypermutation Open
Table S2. Output of 2Â Ă Â 150 Illumina sequencing of HIV-1 and HIV-2 after data processing. For each sample, the numbers of read pairs before and after quality filtering are indicated, both grouped across all amplicons and separated by am…
View article: Additional file 10: of HIV-1 and HIV-2 exhibit similar mutation frequencies and spectra in the absence of G-to-A hypermutation
Additional file 10: of HIV-1 and HIV-2 exhibit similar mutation frequencies and spectra in the absence of G-to-A hypermutation Open
Table S5. Identification and masking of plasmid error hotspots. Plasmid error hotspots (i.e. common sites for background errors due to PCR or sequencing) were identified by examining the distribution of mutation frequencies at every indivi…
View article: Additional file 3: of HIV-1 and HIV-2 exhibit similar mutation frequencies and spectra in the absence of G-to-A hypermutation
Additional file 3: of HIV-1 and HIV-2 exhibit similar mutation frequencies and spectra in the absence of G-to-A hypermutation Open
Dataset S1. HIV-1 and HIV-2 mutation frequencies determined by Illumina sequencing. For each sample, this dataset lists the numbers of reference bases, mutations, mutation frequencies, and relative percentages of many different mutational …
View article: Additional file 6: of HIV-1 and HIV-2 exhibit similar mutation frequencies and spectra in the absence of G-to-A hypermutation
Additional file 6: of HIV-1 and HIV-2 exhibit similar mutation frequencies and spectra in the absence of G-to-A hypermutation Open
Dataset S2. HIV-1 and HIV-2 hypermutant frequencies determined by Illumina sequencing. For each sample, this dataset lists the numbers of total read pairs, hypermutant read pairs, and hypermutation frequencies for all four possible types o…
View article: Additional file 1: of HIV-1 and HIV-2 exhibit similar mutation frequencies and spectra in the absence of G-to-A hypermutation
Additional file 1: of HIV-1 and HIV-2 exhibit similar mutation frequencies and spectra in the absence of G-to-A hypermutation Open
Table S1. Quantification of plasmid carryover from virus production. The levels of HIV-1 or HIV-2 plasmids from transfections remaining in genomic DNA samples were determined using quantitative PCR-based approaches.
View article: Additional file 5: of HIV-1 and HIV-2 exhibit similar mutation frequencies and spectra in the absence of G-to-A hypermutation
Additional file 5: of HIV-1 and HIV-2 exhibit similar mutation frequencies and spectra in the absence of G-to-A hypermutation Open
Table S3. Determination of intra-sample recombination frequencies from PCR. The frequency of intra-sample recombination resulting from PCR was determined using a set of genetic markers that were incorporated into the HIV-1 and HIV-2 plasmi…
View article: Additional file 9: of HIV-1 and HIV-2 exhibit similar mutation frequencies and spectra in the absence of G-to-A hypermutation
Additional file 9: of HIV-1 and HIV-2 exhibit similar mutation frequencies and spectra in the absence of G-to-A hypermutation Open
Table S4. Identification of G-to-A hypermutation hotspots in HIV-1 and HIV-2. G-to-A hypermutation hotspots were identified as statistical upper outliers according to the 1.5Â Ă Â IQR rule. For each hotspot, the relative ranking, position,…
View article: Additional file 11: of HIV-1 and HIV-2 exhibit similar mutation frequencies and spectra in the absence of G-to-A hypermutation
Additional file 11: of HIV-1 and HIV-2 exhibit similar mutation frequencies and spectra in the absence of G-to-A hypermutation Open
Table S6. HIV-1 and HIV-2 primer and barcode sequences for Illumina sequencing.