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1.
J Viral Hepat ; 25(1): 63-71, 2018 01.
Article in English | MEDLINE | ID: mdl-28772350

ABSTRACT

Hepatitis C virus (HCV) is a human hepatotropic virus, but many hepatoma cell lines are not permissive to this virus. In a previous study, we observed that SNU-182, SNU-398 and SNU-449 hepatoma cell lines were nonpermissive to HCV. To understand the nonpermissivity, we evaluated the ability of each cell line to support the different steps of HCV life cycle (entry, replication and production of infectious particles). Using retroviral pseudoparticles pseudotyped with HCV envelope proteins and recombinant HCV produced in cell culture, we observed that low level or absence of claudin-1 (CLDN1) expression limited the viral entry process in SNU-182 and SNU-398 cells, respectively. Our results also showed that supplementation of the three cell lines with miR-122 partly restored the replication of a JFH1 HCV replicon. Finally, we observed that expression of apolipoprotein E (ApoE) was very low or undetectable in the three cell lines and that its ectopic expression permits the production of infectious viral particles in SNU-182 and SNU-398 cells but not in SNU-449 cells. Nevertheless, the supplementation of SNU-182, SNU-398 and SNU-449 cells with CLDN1, miR-122 and ApoE was not sufficient to render these cells as permissive as HuH-7 cells. Thus, these cell lines could serve as cell culture models for functional studies on the role of CLDN1, miR-122 and ApoE in HCV life cycle but also for the identification of new restriction and/or dependency host factors essential for HCV infection.


Subject(s)
Apolipoproteins E/metabolism , Claudin-1/metabolism , Hepacivirus/growth & development , Hepatocytes/physiology , Hepatocytes/virology , MicroRNAs/metabolism , Apolipoproteins E/genetics , Cell Line, Tumor , Claudin-1/genetics , Humans , MicroRNAs/genetics , Transduction, Genetic
2.
J Virol ; 86(1): 584-8, 2012 Jan.
Article in English | MEDLINE | ID: mdl-22013034

ABSTRACT

A deletion of ∼20 amino acids in the stalk of neuraminidase is frequently observed upon transmission of influenza A viruses from waterfowl to domestic poultry. A pair of recombinant H7N1 viruses bearing either a short- or long-stalk neuraminidase was genetically engineered. Inoculation of the long-stalk-neuraminidase virus resulted in a higher cloacal excretion in ducks and led conversely to lower-level oropharyngeal excretion in chickens, associated with a higher-level local immune response and better survival. Therefore, a short-stalk neuraminidase is a determinant of viral adaptation and virulence in chickens but is detrimental to virus replication and shedding in ducks.


Subject(s)
Influenza A Virus, H7N1 Subtype/enzymology , Influenza A Virus, H7N1 Subtype/physiology , Influenza in Birds/virology , Neuraminidase/chemistry , Viral Proteins/chemistry , Virus Shedding , Animals , Chickens , Ducks , Influenza A Virus, H7N1 Subtype/genetics , Neuraminidase/genetics , Neuraminidase/metabolism , Viral Proteins/genetics , Viral Proteins/metabolism , Virus Replication
3.
Transplant Proc ; 41(2): 654-6, 2009 Mar.
Article in English | MEDLINE | ID: mdl-19328947

ABSTRACT

A number of factors interfere with the outcome of renal transplantation. Revealing genetic factors that impact on graft outcome may have consequences for clinical practice. Interleukin-12 (IL-12), by stimulating interferon gamma (IFNgamma) production, plays a crucial role in immune responses against both graft and viral agents. An A-to-C single nucleotide polymorphism (SNP) within the 3'-untranslated region (3'UTR) of the IL-12p40 gene has been reported to be both functionally and clinically relevant. Since the impact of this SNP on kidney graft outcome has never been reported, we investigated the impact of the 3'UTR polymorphism on clinical events after transplantation among 253 kidney recipients transplanted between 1995 and 2003. The polymorphism was genotyped using the restriction fragment length polymorphism method. Our results showed that the 3'UTR polymorphism affected neither graft survival (P = .768) nor the occurrence of delayed graft function (DGF; P = .498). C allele carriers in our study displayed more acute rejections in the first year than patients with the A/A genotype, but it did not reach statistical significance (P = .108). In contrast, the C allele appeared to be a significant risk factor for cytomegalovirus infection (odds ratio = 1.77; P = .027). In conclusion, IL12B 3'UTR polymorphism did not affect graft survival, DGF, or acute rejection episodes, but had an impact on the occurrence of cytomegalovirus infection.


Subject(s)
Interleukin-12 Subunit p40/genetics , Kidney Transplantation/physiology , Polymorphism, Genetic , Polymorphism, Single Nucleotide , 3' Untranslated Regions/genetics , Cadaver , Cytomegalovirus Infections/epidemiology , Cytomegalovirus Infections/genetics , Genotype , Graft Rejection/epidemiology , Graft Rejection/genetics , Graft Survival , Humans , Risk Factors , Tissue Donors , Treatment Outcome , White People
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