Identification of drug resistance and immune-driven variations in hepatitis C virus (HCV) NS3/4A, NS5A and NS5B regions reveals a new approach toward personalized medicine

Ikram, Aqsa; Obaid, Ayesha; Awan, Faryal Mehwish; Hanif, Rumeza; Naz, Anam; Paracha, Rehan Zafar; Ali, Amjad; Janjua, Hussnain Ahmed

doi:10.1016/j.antiviral.2016.10.013

Cited by 8 publications

(5 citation statements)

References 72 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These in silico results have experimental proof. Introduction of RASs in NS3 (Q80, V55I) and NS5B (M423I, V499A) completely prevented recognition of the epitopes associated with HCV clearance by T-cells specific to the wild-type sequences [55,56]. In this context, the appearance of certain RASs within NS5A in treatment naïve patients could reflect an outcome of the successful immune escape contributing to the preferential spread of respective viral variants.…”

Section: Discussionmentioning

confidence: 97%

“…Bioinformatic study by Cuypers L. et al indicated that NS5A harbors clusters of B-and T cell epitopes overlapping regions harboring RAS [54]. In a later study Ikram A. et al explored polymorphic regions of HCV, including RAS in NS3, NS5A, and NS5B, for the presence of CD4+ and CD8+ T cell epitopes, and found several hot spots in which immune and drug selective pressures overlapped [55]. According to Cuypers L. et al, RASs at aa 28 to 32 of NS5A were co-localized with CD4+ T-and B-cell epitopes, and at aa 58-62, with B-cell epitopes (but not with CTL epitopes), whereas conservation showed negative correlation to the presence of T-cell epitopes (immunological constraints), specifically significant for NS5A, also in the regions harboring RAS [54].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Factors Influencing the Prevalence of Resistance-Associated Substitutions in NS5A Protein in Treatment-Naive Patients with Chronic Hepatitis C

et al. 2020

View full text Add to dashboard Cite

Direct-acting antivirals (DAAs) revolutionized treatment of hepatitis C virus (HCV) infection. Resistance-associated substitutions (RASs) present at the baseline impair response to DAA due to rapid selection of resistant HCV strains. NS5A is indispensable target of the current DAA treatment regimens. We evaluated prevalence of RASs in NS5A in DAA-naïve patients infected with HCV 1a (n = 19), 1b (n = 93), and 3a (n = 90) before systematic DAA application in the territory of the Russian Federation. Total proportion of strains carrying at least one RAS constituted 35.1% (71/202). In HCV 1a we detected only M28V (57.9%) attributed to a founder effect. Common RASs in HCV 1b were R30Q (7.5%), L31M (5.4%), P58S (4.4%), and Y93H (5.4%); in HCV 3a, A30S (31.0%), A30K (5.7%), S62L (8.9%), and Y93H (2.2%). Prevalence of RASs in NS5A of HCV 1b and 3a was similar to that worldwide, including countries practicing massive DAA application, i.e., it was not related to treatment. NS5A with and without RASs exhibited different co-variance networks, which could be attributed to the necessity to preserve viral fitness. Majority of RASs were localized in polymorphic regions subjected to immune pressure, with selected substitutions allowing immune escape. Altogether, this explains high prevalence of RAS in NS5A and low barrier for their appearance in DAA-inexperienced population.

show abstract

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Factors Influencing the Prevalence of Resistance-Associated Substitutions in NS5A Protein in Treatment-Naive Patients with Chronic Hepatitis C

et al. 2020

View full text Add to dashboard Cite

show abstract

“…The reference sequences HCV 1a (AB520610), 1b (D10934), 2a (D00944), 3a (AF046866), 3b (D49374), and 6a (AY859526) were obtained from GenBank (NCBI). Based on previous research investigating HCV NS5A DRMs (DCV, LDV, and OMV), the HCV genotype 1a NS5A DRMs were K24E/R/N, M28A/T/G/V, Q30R/K/E/H/L/Y/G/T/D/I, L31M/F, H54R, H58D/P/R, E62D, and Y93H/N/C/S/F/L; the HCV genotype 1b NS5A DRMs were M/L28M/G/T, R30H, L31V/M/F/I, P58S, and Y93H/N/C/S/R; the HCV genotype 2a NS5A DRMs were T24A, L28S/F, L31M/V, C92R, and Y93H; the HCV genotype 3 NS5A DRMs were A30K, L31I/F/M, and Y93H; the HCV genotype 6a NS5A DRMs were Q24H, L31M, P32L/S, and T58A/N/S; and the 8 DRMs for the NS5B inhibitors (SOF) were L159F, T179A, S282T, M289L, I293L, C316N, L320F, and V321I/A …”

Section: Methodsmentioning

confidence: 99%

Naturally occurring antiviral drug resistance in HIV patients who are mono‐infected or co‐infected with HBV or HCV in China

Deng

Liu

et al. 2018

Journal of Medical Virology

View full text Add to dashboard Cite

Drug resistance mutations (DRMs) may reduce the efficacy of antiviral therapy. However, the studies focused on naturally occurring, pre-existing DRMs among co-infected patients in China are limited. To investigate DRMs prevalence in treatment-naïve human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) mono- and co-infected patients in China, a total of 570 patients were recruited for this study. DRMs sequences were amplified and successfully sequenced in 481 of these patients, who were grouped into three cohorts: (i) The HBV cohort included 100 HIV/HBV co-infected and 110 HBV mono-infected patients who were sequenced for HBV; (ii) The HCV cohort included 91 patients who were HIV/HCV co-infected and 72 who were HCV mono-infected for HCV sequencing; and (iii) The HIV cohort included 39 HIV mono-infected, 22 HIV/HCV, and 47 HIV/HBV co-infected patients for HIV sequencing. Next-generation sequencing and Sanger sequencing were used in this study. The results showed that in the HCV cohort, HCV genotypes 6a (P < 0.001) and 3b (P = 0.004) were more prevalent in HIV/HCV co-infected patients, however, the prevalence of HBV and HIV genotypes were similar within the HBV and HIV cohorts. HBV DRMs prevalence was significantly higher in HIV/HBV co-infected than HBV mono-infected patients (8.0% vs 0.9%, P = 0.015), whereas HCV and HIV DRMs did not differ within the HCV and HIV cohort (P > 0.05). This study revealed that HBV DRMs were more prevalent in HIV/HBV co-infected patients in China, while DRMs in HCV and HIV patients did not differ. Further dynamic surveillance of DRMs may be needed.

show abstract

“…Moreover, the World Health Organization (WHO) predicts that drug-resistant diseases could cause 10 million deaths each year by 2050 [53]. Expanding drug resistance is observed in the course of infections such as those caused by gram-positive cocci, e.g., methicillin-resistant Staphylococcus aureus (MRSA), and gram-negative rods, e.g., multidrug-resistant (MDR) Klebsiella pneumoniae, and extensively drug-resistant bacteria (XDR) such as carbapenemase-producing K. pneumoniae or Mycobacterium tuberculosis [54][55][56][57][58][59]. Therefore, the search for novel and innovative analytical and diagnostic methods that will facilitate characterization and elimination of those antibiotic-resistant bacteria is of great significance and is challenging at the same time.…”

Section: Resistance To Antibiotics-an Emerging Problem In Medical and Environmental Microbiologymentioning

confidence: 99%

Physics Comes to the Aid of Medicine—Clinically-Relevant Microorganisms through the Eyes of Atomic Force Microscope

et al. 2020

View full text Add to dashboard Cite

Despite the hope that was raised with the implementation of antibiotics to the treatment of infections in medical practice, the initial enthusiasm has substantially faded due to increasing drug resistance in pathogenic microorganisms. Therefore, there is a need for novel analytical and diagnostic methods in order to extend our knowledge regarding the mode of action of the conventional and novel antimicrobial agents from a perspective of single microbial cells as well as their communities growing in infected sites, i.e., biofilms. In recent years, atomic force microscopy (AFM) has been mostly used to study different aspects of the pathophysiology of noninfectious conditions with attempts to characterize morphological and rheological properties of tissues, individual mammalian cells as well as their organelles and extracellular matrix, and cells’ mechanical changes upon exposure to different stimuli. At the same time, an ever-growing number of studies have demonstrated AFM as a valuable approach in studying microorganisms in regard to changes in their morphology and nanomechanical properties, e.g., stiffness in response to antimicrobial treatment or interaction with a substrate as well as the mechanisms behind their virulence. This review summarizes recent developments and the authors’ point of view on AFM-based evaluation of microorganisms’ response to applied antimicrobial treatment within a group of selected bacteria, fungi, and viruses. The AFM potential in development of modern diagnostic and therapeutic methods for combating of infections caused by drug-resistant bacterial strains is also discussed.

show abstract

Identification of drug resistance and immune-driven variations in hepatitis C virus (HCV) NS3/4A, NS5A and NS5B regions reveals a new approach toward personalized medicine

Cited by 8 publications

References 72 publications

Factors Influencing the Prevalence of Resistance-Associated Substitutions in NS5A Protein in Treatment-Naive Patients with Chronic Hepatitis C

Factors Influencing the Prevalence of Resistance-Associated Substitutions in NS5A Protein in Treatment-Naive Patients with Chronic Hepatitis C

Naturally occurring antiviral drug resistance in HIV patients who are mono‐infected or co‐infected with HBV or HCV in China

Physics Comes to the Aid of Medicine—Clinically-Relevant Microorganisms through the Eyes of Atomic Force Microscope

Contact Info

Product

Resources

About