Silencing HCV Replication in Its Reservoir

Youssef, Samar Samir; Elemeery, Moustafa Nouh; Eldein, Sameh Seif; Ghareeb, Doaa A.

doi:10.3889/oamjms.2018.372

Cited by 7 publications

(6 citation statements)

References 17 publications

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“…Hepatitis E is one of five known human hepatitis viruses. Others are A [5], B [6], [7], C [8], [9], [10] and D [11]. The prevalence of HEV is very low compared with the others, especially hepatitis B virus (HBV).…”

Section: Introductionmentioning

confidence: 99%

Hepatitis E Infection in Nigeria: A Systematic Review

Okagbue¹,

Adamu²,

Bishop³

et al. 2019

Open Access Maced J Med Sci

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BACKGROUND: Research done globally on hepatitis E virus (HEV) infection is far fewer compared with other types of hepatitis virus infection. Little is known on the prevalence of HEV in Nigeria. AIM: The present study presents the prevalence of HEV infection in Nigeria from a few available research papers on HEV. The detailed statistical analysis was used to analyse the prevalence of HEV in humans and animals. MATERIAL AND METHODS: A literature search in Web of Science, Scopus and PubMed databases was done, and a final 7 articles were selected. Minitab 17.0 was used to perform the correlational and binary logistic analyses. RESULTS: Serum and faecal analysis of blood and stool samples of 1178 humans and 210 pigs (animals) were done, and the presence of anti-HEV IgG or HEV RNA in the study samples were 127 and 138 respectively. Further analysis showed the prevalence of HEV are 10.8% and 65.7% in humans and animals, respectively. Weak positive non-significant association (r = 0.327, p-value = 0.474) was obtained between the target (humans and animal) and the HEV infection (positive) groups. The application of binary logistic regression yielded an equation that can be used to predict the target group from the HEV positive humans or animals. Generally, the logistic model was not statistically significant (p-value = 0.376), and the model was able to explain 9.3% of the deviation or variability of the model. The odds ratio is OR = 1.0344 with 0.9550, 1.204 95% Confidence Interval (CI). Thus, in Nigeria, the odds of prevalence of HEV in animals are 1.0344 higher than humans. CONCLUSION: The risk factors obtained from the few available articles are consistent with the global epidemiology of HEV infection. Food and animal handlers and those that consume unsafe water are the key people at risk of HEV infection in Nigeria.

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Section: Introductionmentioning

confidence: 99%

Hepatitis E Infection in Nigeria: A Systematic Review

Okagbue¹,

Adamu²,

Bishop³

et al. 2019

Open Access Maced J Med Sci

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“…Furthermore, several studies have clearly showed that, as in the case of HIV, the simultaneously expression of more than one RNAi sequences is more efficient in blocking viral replication as well as in preventing escape mutations [ 57 , 58 ]. In this context, the simultaneous targeting of viral and host factors involved in viral replication represents a successful strategy in terms of both antiviral effect and prevention of viral mutant selection [ 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 ].…”

Section: Discussionmentioning

confidence: 99%

“…Thus, RNAi might represent a promising therapeutic tool against HCV as targeting viral genome through specific siRNAs should halt viral replication and propagation. Furthermore, it has been previously demonstrated that not only silencing of viral factors, but also interfering with cellular proteins known to play a role in HCV life cycle, would block viral replication [ 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 ]. In particular, it has been shown that combinatorial strategies based on the co-expression of arrays of siRNAs targeting multiple viral and/or cellular genes displayed synergistic anti-HCV effects, hence reducing the possibility of resistant variant emergence [ 13 , 14 , 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

Generation of Combinatorial Lentiviral Vectors Expressing Multiple Anti-Hepatitis C Virus shRNAs and Their Validation on a Novel HCV Replicon Double Reporter Cell Line

Elbadawy

Abdul

Aljuhani

et al. 2020

Viruses

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Despite the introduction of directly acting antivirals (DAAs), for the treatment of hepatitis C virus (HCV) infection, their cost, patient compliance, and viral resistance are still important issues to be considered. Here, we describe the generation of a novel JFH1-based HCV subgenomic replicon double reporter cell line suitable for testing different antiviral drugs and therapeutic interventions. This cells line allowed a rapid and accurate quantification of cell growth/viability and HCV RNA replication, thus discriminating specific from unspecific antiviral effects caused by DAAs or cytotoxic compounds, respectively. By correlating cell number and virus replication, we could confirm the inhibitory effect on the latter of cell over confluency and characterize an array of lentiviral vectors expressing single, double, or triple cassettes containing different combinations of short hairpin (sh)RNAs, targeting both highly conserved viral genome sequences and cellular factors crucial for HCV replication. While all vectors were effective in reducing HCV replication, the ones targeting viral sequences displayed a stronger antiviral effect, without significant cytopathic effects. Such combinatorial platforms as well as the developed double reporter cell line might find application both in setting-up anti-HCV gene therapy approaches and in studies aimed at further dissecting the viral biology/pathogenesis of infection.

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“…23 Continuous treatment with one RNAi molecule could encourage the appearance of several point mutations located inside the specific viral region. 24 To overcome developing viral mutations, multiple RNAi molecules aiming at multiple regions of the HCV genome is recommended, in addition to siRNAs against cellular proteins involved in HCV replication. The value of siRNA as a therapy against HCV infection will depend on establishing effective delivery systems that achieve a long-lasting RNAi activity.…”

Section: Discussionmentioning

confidence: 99%