Cholesterol is important for a post-adsorption step in the entry process of transmissible gastroenteritis virus

Yin, Jun; Glende, Joerg; Schwegmann-Weßels, Christel; Enjuanes, Luis; Herrler, Georg; Ren, Xiaofeng

doi:10.1016/j.antiviral.2010.10.002

Cited by 26 publications

(22 citation statements)

References 44 publications

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“…In the present study, we used a continuous PRRSV-permissive PAM cell line that is considered the primary cell target for PRRSV in the natural host, making it a good system for studying virushost interactions [31]. In a previous study, Yin et al [61] suggested that cholesterol is critical for a post-adsorption step in the entry of TGEV, another porcine alphacoronavirus. Porcine CD163 and APN have been shown to confer permissiveness of non-susceptible cell lines to PRRSV and PEDV, respectively, and have been identified as key molecules in the entry of porcine nidoviruses [9,31,39].…”

Section: Discussionmentioning

confidence: 99%

Cellular cholesterol is required for porcine nidovirus infection

Jeon

Lee

2017

Arch Virol

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Porcine reproductive and respiratory syndrome virus (PRRSV) and porcine epidemic diarrhea virus (PEDV) are porcine nidoviruses that are considered emerging and re-emerging viral pathogens of pigs that pose a significant economic threat to the global pork industry. Although cholesterol is known to affect the replication of a broad range of viruses in vitro, its significance and role in porcine nidovirus infection remains to be elucidated. Therefore, the present study was conducted to determine whether cellular or/and viral cholesterol levels play a role in porcine nidovirus infection. Our results showed that depletion of cellular cholesterol by treating cells with methyl-β-cyclodextrin (MβCD) dose-dependently suppressed the replication of both nidoviruses. Conversely, cholesterol depletion from the viral envelope had no inhibitory effect on porcine nidovirus production. The addition of exogenous cholesterol to MβCD-treated cells moderately restored the infectivity of porcine nidoviruses, indicating that the presence of cholesterol in the target cell membrane is critical for viral replication. The antiviral activity of MβCD on porcine nidovirus infection was found to be predominantly exerted when used as a treatment pre-infection or prior to the viral entry process. Furthermore, pharmacological sequestration of cellular cholesterol efficiently blocked both virus attachment and internalization and, accordingly, markedly affected subsequent post-entry steps of the replication cycle, including viral RNA and protein biosynthesis and progeny virus production. Taken together, our data indicate that cell membrane cholesterol is required for porcine nidovirus entry into cells, and pharmacological drugs that hamper cholesterol-dependent virus entry may have antiviral potential against porcine nidoviruses.

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Section: Discussionmentioning

confidence: 99%

Cellular cholesterol is required for porcine nidovirus infection

Jeon

Lee

2017

Arch Virol

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“…Intestinal epithelial cells (IECs) were maintained with Dulbecco's modified Eagle's F12 Ham medium (DMEM-F12) containing 10% FCS. PEDV strain CV777, TGEV strain PUR46-MAD and vesicular stomatitis virus (VSV) strain Indiana were grown as previously described (Hofmann and Wyler, 1988;Ren et al, 2008;Yin et al, 2010) The following rabbit polyclonal antibodies were generated in our laboratory and used in this study: anti-pAPN, anti-PEDV and anti-TGEV antibodies (Meng et al, 2014;Lv et al, 2014). A monoclonal antibody against the PEDV N protein was also generated in our laboratory.…”

Section: Cells Virus Antisera and Reagentsmentioning

confidence: 99%

Porcine aminopeptidase N mediated polarized infection by porcine epidemic diarrhea virus in target cells

Cong

Bai

et al. 2015

Virology

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a b s t r a c tInfection of polarized intestinal epithelial cells by porcine epidemic diarrhea virus (PEDV) was characterized. Indirect immunofluorescence assay, real-time PCR, and transmission electron microscopy confirmed PEDV can be successfully propagated in immortalized swine small intestine epithelial cells (IECs). Infection involved porcine aminpeptidase N (pAPN), a reported cellular receptor for PEDV, transient expression of pAPN and siRNA targeted pAPN increased and decreased the infectivity of PEDV in IECs, respectively. Subsequently, polarized entry into and release from both Vero E6 and IECs was analyzed. PEDV entry into polarized cells and pAPN grown on membrane inserts occurs via apical membrane. The progeny virus released into the medium was also quantified which demonstrated that PEDV is preferentially released from the apical membrane. Collectively, our data demonstrate that pAPN, the cellular receptor for PEDV, mediates polarized PEDV infection. These results imply the possibility that PEDV infection may proceed by lateral spread of virus in intestinal epithelial cells.

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“…TGE prevalence causes enormous economic losses in pig industry. TGEV is an enveloped, single-stranded, positive-sense RNA virus that belongs to the family Coronaviridae and order Nidovirales Yin et al, 2010). They own the largest RNA viral genome, about 30 kb.…”

Section: Introductionmentioning

confidence: 99%

Phage displayed peptides recognizing porcine aminopeptidase N inhibit transmissible gastroenteritis coronavirus infection in vitro

et al. 2011

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Porcine aminopeptidase N (pAPN) is a cellular receptor of transmissible gastroenteritis virus (TGEV), a porcine coronavirus. Interaction between the spike (S) protein of TGEV and pAPN initiates cell infection. Small molecules, especially peptides are an expanding area for therapy or diagnostic assays for viral diseases. Here, the peptides capable of binding the pAPN were, for the first time, identified by biopanning using a random 12-mer peptide library to the immobilized protein. Three chemically synthesized peptides recognizing the pAPN showed effective inhibition ability to TGEV infection in vitro. A putative TxxF motif was identified in the S protein of TGEV. Phages bearing the specific peptides interacted with the pAPN in ELISA. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assays confirmed the protective effect of the peptides on cell infection by TGEV. Moreover, the excellent immune responses in mice induced by the identified phages provided the possibility to develop novel phage-based vaccines.

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Cholesterol is important for a post-adsorption step in the entry process of transmissible gastroenteritis virus

Cited by 26 publications

References 44 publications

Cellular cholesterol is required for porcine nidovirus infection

Cellular cholesterol is required for porcine nidovirus infection

Porcine aminopeptidase N mediated polarized infection by porcine epidemic diarrhea virus in target cells

Phage displayed peptides recognizing porcine aminopeptidase N inhibit transmissible gastroenteritis coronavirus infection in vitro

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