Identification of HIV Mutation as Diagnostic Biomarker through Next Generation Sequencing

Shaw, Wen Hui; Lin, Qianqian; Muhammad, Zikry Zhiwei Bin Roslee; Lee, Jia Jun; Khong, Wei Xin; Ng, Oon Tek; Tan, Eng Lee

doi:10.7860/jcdr/2016/19760.8140

Cited by 6 publications

(5 citation statements)

References 32 publications

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“…Five of those PR1 mutations (Q7K, L33I, L63I, C67A, and C95A) correspond to experimental mutations introduced to minimize autoproteolysis and to prevent cysteine-thiol oxidation of PR1 (Rosé, Salto, & Craikl, 1993). The three remaining PR1 mutations (K14R, S37N, and R41K) correspond to natural polymorphism mutations that were observed in HIV-1 strains isolated from treatmentnaïve and PI-experienced patients (Shaw et al, 2016;Descamps et al, 2009;Azam, Malik, A c c e p t e d M a n u s c r i p t the PR2 sequence set. This position has been reported as polymorphic with the mutation K57R (Damond et al, 2005).…”

Section: -Results and Discussionmentioning

confidence: 94%

Exploration of the effects of sequence variations between HIV-1 and HIV-2 proteases on their three-dimensional structures

Triki

Kermarrec

Visseaux

et al. 2019

Journal of Biomolecular Structure and Dynamics

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HIV protease inhibitors (PIs) approved by the FDA (US Food and Drug Administration) are a major class of antiretroviral. HIV-2 protease (PR2) is naturally resistant to most of them as PIs were designed for HIV-1 protease (PR1). In this study, we explored the impact of amino-acid substitutions between PR1 and PR2 on the structure of protease (PR) by comparing the structural variability of 13 PR regions using 24 PR1 and PR2 structures complexed with diverse ligands. Our analyses confirmed structural rigidity of the catalytic region and highlighted the important role of three regions in the conservation of the catalytic region conformation. Surprisingly, we showed that the flap region, corresponding to a flexible region, exhibits similar conformations in PR1 and PR2. Furthermore, we identified regions exhibiting different conformations in PR1 and PR2, which could be explained by the intrinsic flexibility of these regions, by crystal packing, or by PR1 and PR2 substitutions. Some substitutions induce structural changes in the R2 and R4 regions that could have an impact on the properties of the PI-binding site and could thus modify PI binding mode. Substitutions involved in structural changes in the elbow region could alter the flexibility of the PR2 flap regions relative to PR1, and thus play a role in the transition from the semi-open form to the closed form, and have an impact on ligand binding. These results improve the understanding of the impact of sequence variations between PR1 and PR2 on the natural resistance of HIV-2 to commercially available PIs.

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Section: -Results and Discussionmentioning

confidence: 94%

Exploration of the effects of sequence variations between HIV-1 and HIV-2 proteases on their three-dimensional structures

Triki

Kermarrec

Visseaux

et al. 2019

Journal of Biomolecular Structure and Dynamics

View full text Add to dashboard Cite

show abstract

“…For instance, it was recently shown that NGS provides more precise HIV diagnosis with a better discrimination between different genotypes (Shaw et al . 2016 ). Furthermore, it can provide very high sensitivity for the diagnostics of rare pathogens, as shown with the identification of Leptospira as the causative agent of encephalitis after the failure of 38 different diagnostic tests (Wilson et al .…”

Section: Trends In Ngsmentioning

confidence: 99%

Recent trends in molecular diagnostics of yeast infections: from PCR to NGS

Gabaldón

2019

FEMS Microbiology Reviews

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The incidence of opportunistic yeast infections in humans has been increasing over recent years. These infections are difficult to treat and diagnose, in part due to the large number and broad diversity of species that can underlie the infection. In addition, resistance to one or several antifungal drugs in infecting strains is increasingly being reported, severely limiting therapeutic options and showcasing the need for rapid detection of the infecting agent and its drug susceptibility profile. Current methods for species and resistance identification lack satisfactory sensitivity and specificity, and often require prior culturing of the infecting agent, which delays diagnosis. Recently developed high-throughput technologies such as next generation sequencing or proteomics are opening completely new avenues for more sensitive, accurate and fast diagnosis of yeast pathogens. These approaches are the focus of intensive research, but translation into the clinics requires overcoming important challenges. In this review, we provide an overview of existing and recently emerged approaches that can be used in the identification of yeast pathogens and their drug resistance profiles. Throughout the text we highlight the advantages and disadvantages of each methodology and discuss the most promising developments in their path from bench to bedside.

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“…The common mutations identified at virus are located on the pol gene that codes for reverse transcriptase subunits [22]. Unlike other silent mutations, the missense mutation has more implications.…”

Section: Identification Of the Novel Biomarkers Through Ngsmentioning

confidence: 99%

Explore the Novel Biomarkers through Next-Generation Sequencing

2018

Genotyping

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Next-generation sequencing is being a robust technology for the practice of clinical diagnosis. The reason is that this technology offers the advantage of higher sensitivity and the potential to detect the full genome sequence of pathogens, including unknown pathogen species. In view of the exceptional advantages of next-generation sequencing, the technology can be used to improve and revolutionize conventional pathogenic detection methodologies. The technological result holds great possibilities in helping to support clinicians with richer insights into host's genomic features, including the appropriateness to drug resistance based on the sequencing mapping of the microorganism. Besides, the technology will help discover the source of infection and insights into treatment directions, furthermore lead to the advancements in diagnosis. Eventually, this technology will benefit the clinical community in infectious disease prediction and prevention.

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Identification of HIV Mutation as Diagnostic Biomarker through Next Generation Sequencing

Cited by 6 publications

References 32 publications

Exploration of the effects of sequence variations between HIV-1 and HIV-2 proteases on their three-dimensional structures

Exploration of the effects of sequence variations between HIV-1 and HIV-2 proteases on their three-dimensional structures

Recent trends in molecular diagnostics of yeast infections: from PCR to NGS

Explore the Novel Biomarkers through Next-Generation Sequencing

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