Subcellular Localization of Hepatitis C Virus Structural Proteins in a Cell Culture System That Efficiently Replicates the Virus

Rouillé, Yves; Helle, François; Delgrange, David; Roingeard, Philippe; Voisset, Cécile; Blanchard, Emmanuelle; Belouzard, Sandrine; McKeating, Jane A.; Patel, Arvind H.; Maertens, Geert; Wakita, Takaji; Wychowski, Czeslaw; Dubuisson, Jean

doi:10.1128/jvi.80.6.2832-2841.2006

Cited by 177 publications

(188 citation statements)

References 40 publications

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“…At the indicated time, cells were fixed with 3 % paraformaldehyde and then permeabilized with 0.1 % Triton X-100 (Sigma-Aldrich) in PBS. Immunolabelling and confocal microscopy were performed as described previously (Rouillé et al, 2006).…”

Section: Methodsmentioning

confidence: 99%

Identification of a dominant endoplasmic reticulum-retention signal in yellow fever virus pre-membrane protein

Ciczora

Callens

Séron

et al. 2009

Journal of General Virology

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Yellow fever virus (YFV) encodes two envelope proteins, pre-membrane (prM) and envelope (E), that accumulate in the endoplasmic reticulum (ER). The C termini of prM and E form two antiparallel transmembrane a-helices that contain ER-retention signals. To understand further the ER retention of the prME heterodimer, we characterized the subcellular localization of chimeric proteins made of a reporter protein fused to the transmembrane segments of YFV envelope proteins. We showed that at least three of the transmembrane segments of the prME heterodimer are ER-retention signals. Interestingly, increasing the length of these a-helices led to the export of the chimeric proteins out of the ER. Furthermore, adding a diacidic export signal at the C terminus of the first transmembrane segment of the E protein also induced export to the cell surface. However, adding this export signal at the C terminus of the first transmembrane segment of E in the context of prME did not change the subcellular localization of the prME heterodimer, suggesting the presence of a stronger ER-retention signal outside the first transmembrane segment of E. Importantly, the diacidic export motif added to the C terminus of the first transmembrane segment of the prM protein was not sufficient to export a chimeric protein out of the ER, indicating that this sequence is a dominant ER-retention signal. Together, these data indicate that a combination of several signals of different strengths contributes to the ER retention of the YFV envelope protein heterodimer.

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Section: Methodsmentioning

confidence: 99%

Identification of a dominant endoplasmic reticulum-retention signal in yellow fever virus pre-membrane protein

Ciczora

Callens

Séron

et al. 2009

Journal of General Virology

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“…21 The plasmid pJFH1, 5 containing the full-length cDNA of JFH1 isolate and kindly provided by T. Wakita (Tokyo Metropolitan Institute for Neuroscience, Japan) was used to generate HCVcc as described. 24 HCVcc stock used in our experiments was produced in DMEM containing 5% LPDS.…”

Section: Methodsmentioning

confidence: 99%

Serum amyloid A has antiviral activity against hepatitis C virus by inhibiting virus entry in a cell culture system

et al. 2006

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Serum amyloid A (SAA) is an acute phase protein produced by the liver. SAA concentration increases markedly in the serum following inflammation and infection. Large increases in SAA concentration during the acute phase response suggest that SAA has a beneficial role in host defense. This study sought to determine the effect of SAA on hepatitis C virus (HCV) infectivity using retroviral particles pseudotyped with HCV envelope glycoproteins (HCVpp) and the recently developed cell culture system for HCV (HCVcc). SAA inhibited HCVpp and HCVcc infection in a dose-dependent manner by affecting an early step of the virus life cycle. Further characterization with HCVpp indicated that SAA blocks virus entry by interacting with the viral particle. In addition, the antiviral activity of SAA was strongly reduced when high-density lipoproteins (HDL) were coincubated with SAA. However, HDL had only a slight effect on the antiviral activity of SAA when HCVpp was first preincubated with SAA. Furthermore, analyses of SAA in sera of chronic HCV patients revealed the presence of variable levels of SAA with abnormally elevated concentrations in some cases. However, no obvious clinical correlation was found between SAA levels and HCV viral loads. In conclusion, our data demonstrate an antiviral activity for SAA and suggest a tight relationship between SAA and HDL in modulating HCV infectivity. Supplementary material for this article can be found on the HEPATOLOGY website (http://interscience.wiley.com/ jpages/0270-9139/suppmat/index.html).

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“…Although it is not yet clear whether PML has a role in antiviral defence against LCMV and RABV, it may be significant that the LCMV Z protein and the RABV P protein, as well as smaller truncated products, interact with PML to cause a reorganization of PML nuclear bodies (Borden et al, 1998a, b;Djavani et al, 2001;Blondel et al, 2002). HCV core protein can co-localize with PML and p53 in PML nuclear bodies (Herzer et al, 2005), although the relevance of this is debated (Rouille et al, 2006).…”

Section: General Considerations Of How Viruses Evade the Ifn Responsementioning

confidence: 99%

Interferons and viruses: an interplay between induction, signalling, antiviral responses and virus countermeasures

Randall

Goodbourn

2008

Journal of General Virology

1,373

1,420

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The interferon (IFN) system is an extremely powerful antiviral response that is capable of controlling most, if not all, virus infections in the absence of adaptive immunity. However, viruses can still replicate and cause disease in vivo, because they have some strategy for at least partially circumventing the IFN response. We reviewed this topic in 2000 [Goodbourn, S., Didcock, L. & Randall, R. E. (2000). J Gen Virol 81, 2341-2364] but, since then, a great deal has been discovered about the molecular mechanisms of the IFN response and how different viruses circumvent it. This information is of fundamental interest, but may also have practical application in the design and manufacture of attenuated virus vaccines and the development of novel antiviral drugs. In the first part of this review, we describe how viruses activate the IFN system, how IFNs induce transcription of their target genes and the mechanism of action of IFN-induced proteins with antiviral action. In the second part, we describe how viruses circumvent the IFN response. Here, we reflect upon possible consequences for both the virus and host of the different strategies that viruses have evolved and discuss whether certain viruses have exploited the IFN response to modulate their life cycle (e.g. to establish and maintain persistent/latent infections), whether perturbation of the IFN response by persistent infections can lead to chronic disease, and the importance of the IFN system as a species barrier to virus infections. Lastly, we briefly describe applied aspects that arise from an increase in our knowledge in this area, including vaccine design and manufacture, the development of novel antiviral drugs and the use of IFN-sensitive oncolytic viruses in the treatment of cancer. Biology of the interferon systemThe interferons (IFNs) are a group of secreted cytokines that elicit distinct antiviral effects. They are grouped into three classes called type I, II and III IFNs, according to their amino acid sequence. Type I IFNs (discovered in 1957;Isaacs & Lindenmann, 1957) comprise a large group of molecules; mammals have multiple distinct IFN-a genes (13 in man), one to three IFN-b genes (one in man) and other genes, such as IFN-v, -e, -t, -d and -k. The IFN-a and -b genes are induced directly in response to viral infection, whereas IFN-v, -e, -d and -k play less well-defined roles, such as regulators of maternal recognition in pregnancy. Thus, rather than use the term 'type I IFN', we will use IFN-a/b when referring to the virally induced cytokines. Although the multigenic nature of IFN-a has been known for over 20 years, the significance of this is still debatedi.e. whether these genes are expressed differentially in distinct cell types, whether they are inducible by different types of viruses or whether they are functionally specialized (Brideau-Andersen et al., 2007). For the rest of this review, we will not distinguish between IFN-a subtypes. Type III IFNs have been described more recently and comprise IFNl1, -l2 and -l3, also referred to as IL-2...

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Subcellular Localization of Hepatitis C Virus Structural Proteins in a Cell Culture System That Efficiently Replicates the Virus

Cited by 177 publications

References 40 publications

Identification of a dominant endoplasmic reticulum-retention signal in yellow fever virus pre-membrane protein

Identification of a dominant endoplasmic reticulum-retention signal in yellow fever virus pre-membrane protein

Serum amyloid A has antiviral activity against hepatitis C virus by inhibiting virus entry in a cell culture system

Interferons and viruses: an interplay between induction, signalling, antiviral responses and virus countermeasures

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