Defined host factors support HBV infection in non‐hepatic 293T cells

Yang, Xiaoqiang; Cai, Wei-Wen; Sun, Xiaoyue; Bi, Yong‐Mei; Zeng, Chui; Zhao, Xiaoyu; Zhou, Qi; Xu, Tian; Xie, Qiang; Sun, Pingnan; Zhou, Xiaoling

doi:10.1111/jcmm.14944

Cited by 6 publications

(7 citation statements)

References 42 publications

(95 reference statements)

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“…The results obtained by Yang et al, indicated that this cell culture model supports HBV entry, transcription, and replication, as evidenced by the detection of HBV pgRNA, HBV cccDNA, HBsAG, HBeAg, HBcAg and HBV DNA. Interestingly, these 293T-NE-3NRs cells were successfully infected with HBV even at low GEq which mimics natural physiological conditions more accurately [ 62 ]. Contrary to HBV, HDV does not seem to require the expression of these hepatocyte-enriched transcription factors.…”

Section: In Vitro Model Systems Based On Engineered Non-hepatic Cell Linesmentioning

confidence: 99%

Cell Culture Models for the Study of Hepatitis D Virus Entry and Infection

Heuschkel

Baumert

2021

Viruses

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Chronic hepatitis D is one of the most severe and aggressive forms of chronic viral hepatitis with a high risk of developing hepatocellular carcinoma (HCC). It results from the co-infection of the liver with the hepatitis B virus (HBV) and its satellite, the hepatitis D virus (HDV). Although current therapies can control HBV infection, no treatment that efficiently eliminates HDV is available and novel therapeutic strategies are needed. Although the HDV cycle is well described, the lack of simple experimental models has restricted the study of host–virus interactions, even if they represent relevant therapeutic targets. In the last few years, the discovery of the sodium taurocholate co-transporting polypeptide (NTCP) as a key cellular entry factor for HBV and HDV has allowed the development of new cell culture models susceptible to HBV and HDV infection. In this review, we summarize the main in vitro model systems used for the study of HDV entry and infection, discuss their benefits and limitations and highlight perspectives for future developments.

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Section: In Vitro Model Systems Based On Engineered Non-hepatic Cell Linesmentioning

confidence: 99%

Cell Culture Models for the Study of Hepatitis D Virus Entry and Infection

Heuschkel

Baumert

2021

Viruses

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“…Yang et al . reported that infection of HEK293 cells with HBV requires the introduction of NTCP and at least three additional factors (HNF4a, PPARa and RxRa) 48 while this remains unknown for other, harder to transfect cell types. Using IVT mRNA may help to overcome this problem because it allows highly efficient introduction of multiple proteins simultaneously 26 or consecutively.…”

Section: Discussionmentioning

confidence: 99%

Concentration of Na+-taurocholate-cotransporting polypeptide expressed after in vitro-transcribed mRNA transfection determines susceptibility of hepatoma cells for hepatitis B virus

Oswald

Chakraborty

et al. 2021

Sci Rep

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Infection of hepatocytes by hepatitis B virus (HBV) depends on surface expression of its receptor Na+-taurocholate-cotransporting polypeptide (NTCP), but sufficient NTCP expression is lacking in most cell lines. NTCP can be introduced by plasmid transfection or transduction by viral vectors to render cells permissive for HBV. However, transient transfection of hepatocyte-derived cell lines is inefficient, resulting in inhomogeneous protein expression and does not allow to adapt the level of NTCP expression. We therefore utilized in vitro transcribed mRNA to introduce NTCP into cells. Optimization using alternative cap structures and nucleotide modifications rendered mRNA transfection into different non-hepatic and hepatic cell lines very efficient. After transfection of mRNA, surface expression and functionality of NTCP was demonstrated by staining with an N-terminal HBV-preS peptide and bile acid uptake. Introduction of NTCP by mRNA transfection increased susceptibility of hepatoma cells to HBV in a dose-dependent manner. Transfection of NTCP mRNA into non-liver cells, in contrast, supported bile acid uptake but did still not render the cells permissive for HBV, demonstrating the requirement for additional host factors. Introduction of candidate host factors by mRNA transfection will allow for fast and convenient analysis of the viral life cycle using a transient, but reliable expression system.

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“…In contrast to HBV, HDV infection is predominantly determined at the receptor level [ 55 ]. Ectopic expression of human NTCP is enough to confer cells from different tissue and species susceptibility for HDV, whereas additional host factors besides NTCP are required for successful HBV infection [ 55 , 56 ]. HDV RNA replication is entirely independent of the helper virus.…”

Section: Helper Virus’s Functionsmentioning

confidence: 99%

HDV-Like Viruses

Pérez‐Vargas

Oliveira

Jacquet

et al. 2021

Viruses

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Hepatitis delta virus (HDV) is a defective human virus that lacks the ability to produce its own envelope proteins and is thus dependent on the presence of a helper virus, which provides its surface proteins to produce infectious particles. Hepatitis B virus (HBV) was so far thought to be the only helper virus described to be associated with HDV. However, recent studies showed that divergent HDV-like viruses could be detected in fishes, birds, amphibians, and invertebrates, without evidence of any HBV-like agent supporting infection. Another recent study demonstrated that HDV can be transmitted and propagated in experimental infections ex vivo and in vivo by different enveloped viruses unrelated to HBV, including hepatitis C virus (HCV) and flaviviruses such as Dengue and West Nile virus. All this new evidence, in addition to the identification of novel virus species within a large range of hosts in absence of HBV, suggests that deltaviruses may take advantage of a large spectrum of helper viruses and raises questions about HDV origins and evolution.

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Defined host factors support HBV infection in non‐hepatic 293T cells

Cited by 6 publications

References 42 publications

Cell Culture Models for the Study of Hepatitis D Virus Entry and Infection

Cell Culture Models for the Study of Hepatitis D Virus Entry and Infection

Concentration of Na+-taurocholate-cotransporting polypeptide expressed after in vitro-transcribed mRNA transfection determines susceptibility of hepatoma cells for hepatitis B virus

HDV-Like Viruses

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