HCV envelope protein function is dependent on the peptides preceding the glycoproteins

Bian, Tao; Zhou, Youwen; Bi, Shengli; Tan, Wenjie; Wang, Yue

doi:10.1016/j.bbrc.2008.11.024

Cited by 13 publications

(13 citation statements)

References 26 publications

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“…Our data is in agreement with Zekri et al, 2009 [41], who demonstrated that siRNAs against 5'UTR of HCV genotype-4 inhibited HCV replication in serum infected Huh-7 cells. Bian et al, 2009 [54] reported that 14 amino acids from the C-terminus of Core gene are required for proper function of E1 and at least 12 amino acids from C-terminus of E1 genes are required for E2 function, influencing the proper glycosylation of E1 and E2 gene. Effect of HCV-3a Core siRNA on HCV viral titer reduction is possibly due to the interaction between different HCV regions and may also due to the simultaneous degradation of HCV genomic RNA (as HCV genome contains a positive sense ssRNA).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of core gene of HCV 3a genotype using synthetic and vector derived siRNAs

Khaliq

Saleem

Ijaz

et al. 2010

Virol J

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BackgroundHepatitis C virus (HCV) is a major causative agent of liver associated diseases throughout the world, with genotype 3a responsible for most of the cases in Pakistan. Due to the limited efficiency of current therapy, RNA interference (RNAi) a novel regulatory and powerful silencing approach for molecular therapeutics through a sequence-specific RNA degradation process represents an alternative option.ResultsThe current study was purposed to assess and explore the possibility of RNAi to silence the HCV-3a Core gene expression, which play complex role in regulation of cell growth and host genes expression essential for infectivity and disease progression. To identify the potent siRNA target sites, 5 small interfering RNAs (siRNAs) against Core gene were designed and in vitro transcribed after consensus sequence analysis of different HCV-3a isolates. Antiviral effects of siRNAs showed upto 80% inhibition of Core gene expression by different siRNAs into Huh-7 cells as compared with Mock transfected and control siRNAs treated cells. For long lasting effect of siRNAs, vector based short hairpin siRNAs (shRNAs) were designed and tested against HCV-3a Core which resulted in a similar pattern of inhibition on RNA and protein expression of HCV Core as synthetic siRNAs. Furthermore, the efficacy of cell culture tested siRNA and shRNA, were evaluated for inhibition of HCV replication in HCV infected serum inoculated Huh-7 cells and a significant decrease in HCV viral copy number was observed.ConclusionsOur results support the possibility of using consensus siRNA and shRNA-based molecular therapy as a promising strategy in effective inhibition of HCV-3a genotype.

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Section: Discussionmentioning

confidence: 99%

Inhibition of core gene of HCV 3a genotype using synthetic and vector derived siRNAs

Khaliq

Saleem

Ijaz

et al. 2010

Virol J

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“…Retrovirus-based influenza HA/NA pseudoparticle systems have been demonstrated to accurately represent the biology of the corresponding wild-type viruses [17]–[21], [29], [30]. For research on HPAI viruses, the use of pseudoparticle systems eliminates not only routine biosafety issues but also the possibility of production of a manmade, highly pathogenic virus.…”

Section: Discussionmentioning

confidence: 99%

Characterization of Neuraminidases from the Highly Pathogenic Avian H5N1 and 2009 Pandemic H1N1 Influenza A Viruses

Zhang

Wang

et al. 2010

PLoS ONE

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To study the precise role of the neuraminidase (NA), and its stalk region in particular, in the assembly, release, and entry of influenza virus, we deleted the 20-aa stalk segment from 2009 pandemic H1N1 NA (09N1) and inserted this segment, now designated 09s60, into the stalk region of a highly pathogenic avian influenza (HPAI) virus H5N1 NA (AH N1). The biological characterization of these wild-type and mutant NAs was analyzed by pseudotyped particles (pseudoparticles) system. Compared with the wild-type AH N1, the wild-type 09N1 exhibited higher NA activity and released more pseudoparticles. Deletion/insertion of the 09s60 segment did not alter this relationship. The infectivity of pseudoparticles harboring NA in combination with the hemagglutinin from HPAI H5N1 (AH H5) was decreased by insertion of 09s60 into AH N1 and was increased by deletion of 09s60 from 09N1. When isolated from the wild-type 2009H1N1 virus, 09N1 existed in the forms (in order of abundance) dimer>>tetramer>monomer, but when isolated from pseudoparticles, 09N1 existed in the forms dimer>monomer>>>tetramer. After deletion of 09s60, 09N1 existed in the forms monomer>>>dimer. AH N1 from pseudoparticles existed in the forms monomer>>dimer, but after insertion of 09s60, it existed in the forms dimer>>monomer. Deletion/insertion of 09s60 did not alter the NA glycosylation pattern of 09N1 or AH N1. The 09N1 was more sensitive than the AH N1 to the NA inhibitor oseltamivir, suggesting that the infectivity-enhancing effect of oseltamivir correlates with robust NA activity.

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“…The lack of upstream peptides in proteins E1 and E2 is likely to affect their anchoring to the ER membrane, and in turn their glycosylation, folding, and heterodimerization, eventually leading to reduced infectivity. Using HCVpp, Bian et al (Bian et al, 2009) demonstrated that at least 14 amino acids from the core C-terminus are required for E1 function and that at least 12 amino acids from the E1 C-terminus are required for E2 function. These peptides appear to influence the glycosylation of E1 and E2.…”

Section: Hcv Pseudotyped Particle (Hcvpp)mentioning

confidence: 99%

Cellular models for the screening and development of anti-hepatitis C virus agents

Gondeau

Pichard-Garcia

Maurel

2009

Pharmacology & Therapeutics

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Investigations on the biology of hepatitis C virus (HCV) have been hampered by the lack of small animal models. Efforts have therefore been directed to designing practical and robust cellular models of human origin able to support HCV replication and production in a reproducible, reliable and consistent manner. Many different models based on different forms of virions and hepatoma or other cell types have been described including virus-like particles, pseudotyped particles, subgenomic and full length replicons, virion productive replicons, immortalised hepatocytes, fetal and adult primary human hepatocytes. This review focuses on these different cellular models, their advantages and disadvantages at the biological and experimental levels, and their respective use for evaluating the effect of antiviral molecules on different steps of HCV biology including virus entry, replication, particles generation and excretion, as well as on the modulation by the virus of the host cell response to infection.

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HCV envelope protein function is dependent on the peptides preceding the glycoproteins

Cited by 13 publications

References 26 publications

Inhibition of core gene of HCV 3a genotype using synthetic and vector derived siRNAs

Inhibition of core gene of HCV 3a genotype using synthetic and vector derived siRNAs

Characterization of Neuraminidases from the Highly Pathogenic Avian H5N1 and 2009 Pandemic H1N1 Influenza A Viruses

Cellular models for the screening and development of anti-hepatitis C virus agents

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