Characterization of a Porcine Lung Epithelial Cell Line Suitable for Influenza Virus Studies

Seo, Sang Heui; Goloubeva, Olga; Webby, Richard J.; Webster, Robert G.

doi:10.1128/jvi.75.19.9517-9525.2001

Cited by 64 publications

(45 citation statements)

References 41 publications

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“…Compared to the pretreatment isolate, this virus had a drugresistant mutation in the NA catalytic site (R152K) and a mutation in the region of the HA receptor-binding site (T198I). The HA mutation increased the virus binding to 3-linked receptors and, as a result, to MDCK cells which express high quantities of 3-linked sialic acids (21,33). Enhanced binding to cells increased the virus dependence on the NA activity, thereby masking the drug-resistant effect of the NA mutation.…”

Section: Discussionmentioning

confidence: 99%

“…It is therefore believed that in order to adequately assay human influenza virus sensitivity to NAI, a cell line is required which supports efficient growth of clinical influenza virus isolates and expresses large amounts of 6-linked sialic acids and small amounts of 3-linked sialic acids (38). Unfortunately, the concentration of 6-linked sialic acids in continuous cell lines used for propagation of influenza viruses in the laboratory (such as MDCK and VERO cells) is relatively low and is comparable to the concentration of 3-linked sialic acids (16,21,33).…”

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confidence: 99%

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Overexpression of the α-2,6-Sialyltransferase in MDCK Cells Increases Influenza Virus Sensitivity to Neuraminidase Inhibitors

Matrosovich

Carr

et al. 2003

J Virol

336

302

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No reliable cell culture assay is currently available for monitoring human influenza virus sensitivity to neuraminidase inhibitors (NAI). This can be explained by the observation that because of a low concentration of sialyl-␣2,6-galactose (Sia[␣2,6]Gal)-containing virus receptors in conventional cell lines, replication of human virus isolates shows little dependency on viral neuraminidase. To test whether overexpression of Sia(␣2,6)Gal moieties in cultured cells could make them suitable for testing human influenza virus sensitivity to NAI, we stably transfected MDCK cells with cDNA of human 2,6-sialyltransferase (SIAT1). Transfected cells expressed twofold-higher amounts of 6-linked sialic acids and twofold-lower amounts of 3-linked sialic acids than parent MDCK cells as judged by staining with Sambucus nigra agglutinin and Maackia amurensis agglutinin, respectively. After transfection, binding of a clinical human influenza virus isolate was increased, whereas binding of its egg-adapted variant which preferentially bound 3-linked receptors was decreased. The sensitivity of human influenza A and B viruses to the neuraminidase inhibitor oseltamivir carboxylate was substantially improved in the SIAT1-transfected cell line and was consistent with their sensitivity in neuraminidase enzyme assay and with the hemagglutinin (HA) receptor-binding phenotype. MDCK cells stably transfected with SIAT1 may therefore be a suitable system for testing influenza virus sensitivity to NAI.The neuraminidase (NA) of influenza A and B viruses cleaves the ␣-glycosidic linkages between sialic acid and the adjacent sugar and thus destroys virus receptors on the cell surface, extracellular inhibitors, and viral glycoproteins (reviewed in references 2 and 8). The NA activity is believed to be particularly important at the late stages of infection by preventing hemagglutinin (HA)-mediated self-aggregation and facilitating release of progeny virions from cells. Interaction of virions with cell-associated and soluble sialylglycoconjugates of the host is mediated by HA and NA in an antagonistic manner, which has to be carefully balanced to allow efficient virus replication (reviewed in reference 36).With increasing use of neuraminidase inhibitors (NAI) for influenza treatment, there is a need for a suitable methodology to monitor for emergence of virus resistance (32,34,38). In cell culture experiments, resistance to NAI results from mutation of either HA, NA, or both glycoproteins. Mutations in HA usually precede NA mutations and reduce virus affinity for sialic acid-containing receptors, thereby decreasing the dependency of the virus on NA function, whereas mutations in NA decrease the binding affinity of the inhibitor to the catalytic site (reviewed in references 19, 29, and 30). In a clinical setting, NA-mediated resistance seems to be the primary mechanism of resistance to NAI and can be easily and reliably monitored using an in vitro enzyme inhibition assay (32,34,38). Since the possibility cannot be excluded that the loss of sensitivit...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Overexpression of the α-2,6-Sialyltransferase in MDCK Cells Increases Influenza Virus Sensitivity to Neuraminidase Inhibitors

Matrosovich

Carr

et al. 2003

J Virol

336

302

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“…Several cell lines such as Madin Darby canine kidney (MDCK) cells [4,6,7], African green monkey kidney Vero cells [28], human retina-derived cell line Per.C6 [29] and St. Jude porcine lung cells (SJPL) [30] have been tested for the production of influenza vaccines. While all those cell lines have major advantages towards the conventional egg-based vaccine production method, MDCK cell line is arguably the best-characterized cell culture system for influenza virus replication [9].…”

Section: Page | 24mentioning

confidence: 99%

Canine MDCK cell lines are refractory to infection with human and mouse prions

Polymenidou

Trusheim

Stallmach

et al. 2008

Vaccine

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“…It should, however, be noted that some characteristics of porcine embryonic stem cells differ from murine and ovine embryos (Piedrahita et al, 1990). Cell lines can be used for some diseases, for example post-weaning diarrhoea (Pavlova et al, 2008) and the influenza virus (Seo et al, 2001), but this aspect will not be discussed further in this review.…”

Section: Introductionmentioning

confidence: 99%

Porcine models for the metabolic syndrome, digestive and bone disorders: a general overview

Litten-Brown

Corson

Clarke

2010

Animal

147

136

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The aim of this review article is to provide an overview of the role of pigs as a biomedical model for humans. The usefulness and limitations of porcine models have been discussed in terms of metabolic, cardiovascular, digestive and bone diseases in humans. Domestic pigs and minipigs are the main categories of pigs used as biomedical models. One drawback of minipigs is that they are in short supply and expensive compared with domestic pigs, which in contrast cost more to house, feed and medicate. Different porcine breeds show different responses to the induction of specific diseases. For example, ossabaw minipigs provide a better model than Yucatan for the metabolic syndrome as they exhibit obesity, insulin resistance and hypertension, all of which are absent in the Yucatan. Similar metabolic/physiological differences exist between domestic breeds (e.g. Meishan v. Pietrain). The modern commercial (e.g. Large White) domestic pig has been the preferred model for developmental programming due to the 2-to 3-fold variation in body weight among littermates providing a natural form of foetal growth retardation not observed in ancient (e.g. Meishan) domestic breeds. Pigs have been increasingly used to study chronic ischaemia, therapeutic angiogenesis, hypertrophic cardiomyopathy and abdominal aortic aneurysm as their coronary anatomy and physiology are similar to humans. Type 1 and II diabetes can be induced in swine using dietary regimes and/or administration of streptozotocin. Pigs are a good and extensively used model for specific nutritional studies as their protein and lipid metabolism is comparable with humans, although pigs are not as sensitive to protein restriction as rodents. Neonatal and weanling pigs have been used to examine the pathophysiology and prevention/treatment of microbial-associated diseases and immune system disorders. A porcine model mimicking various degrees of prematurity in infants receiving total parenteral nutrition has been established to investigate gut development, amino acid metabolism and non-alcoholic fatty liver disease. Endoscopic therapeutic methods for upper gastrointestinal tract bleeding are being developed. Bone remodelling cycle in pigs is histologically more similar to humans than that of rats or mice, and is used to examine the relationship between menopause and osteoporosis. Work has also been conducted on dental implants in pigs to consider loading; however with caution as porcine bone remodels slightly faster than human bone. We conclude that pigs are a valuable translational model to bridge the gap between classical rodent models and humans in developing new therapies to aid human health.

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Characterization of a Porcine Lung Epithelial Cell Line Suitable for Influenza Virus Studies

Cited by 64 publications

References 41 publications

Overexpression of the α-2,6-Sialyltransferase in MDCK Cells Increases Influenza Virus Sensitivity to Neuraminidase Inhibitors

Overexpression of the α-2,6-Sialyltransferase in MDCK Cells Increases Influenza Virus Sensitivity to Neuraminidase Inhibitors

Canine MDCK cell lines are refractory to infection with human and mouse prions

Porcine models for the metabolic syndrome, digestive and bone disorders: a general overview

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