HeLa cell lines producing infectious replication-defective HIV virions with varyinggp160 densities indicate that increasing cellulargp160 levels cause an increase in cell-to-cell fusion, while increasing viralgp160 levels exert a biphasic effect on infectivity
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HeLa cell lines producing infectious replication-defective HIV virions with varying gp160 densities indicate that increasing cellular gp160 levels cause an increase in cell-to-cell fusion, while increasing viral gp160 levels exert a biphasic effect on infectivityAbstract
Although the density of the HIV envelope protein (gp160) can vary on cells and virions, there has been little investigation into how the levels affect HIV infection and cell-to-cell fusion. To address this several cell lines stably producing infectious, replication defective virions of the T-cell line adapted HIV isolate, HXB2, were made. The cell lines varied from one another in gp160 surface expression over a five-fold range, while expressing similar levels of the Gag polyprotein. As a consequence, the cell lines collectively produced virus that varied in gp160 content over a six-fold range. With the cell lines it was observed that increasing gp160 surface expression increases cell-to-cell fusion efficiency and syncytium size. With the virus preparations it was found that gp160 levels had a biphasic affect on infection efficiency. Virus preparations with gp160 levels of 10-30 molecules per virion showed that increased gp160 content correlated with increased infection efficiency. However, at gp160 levels above 50 molecules per virion there was a decrease in infection efficiency associated with increasing gp160 per virion content. Therefore, it appears that increasing gp160 surface density exerts a qualitatively different affect on infection and cell-to-cell fusion. Based upon functional analysis, several cell lines producing the gp160 molecule from the primary isolate, JR-FL were also made. These cell lines were less characterized, and yet have the potential to be useful reagents in HIV research as well.Description
University of Maryland, Baltimore. Molecular and Cell Biology. Ph.D. 1999Keyword
Biology, MolecularBiology, Cell
Biology, Microbiology
infection efficiency
HeLa Cells
HIV Envelope Protein gp160
Virion
Identifier to cite or link to this item
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NSAIDs and cardiovascular adverse events: Is increasing risk associated with increasing Cox-II selectivity ratios?Slagle, Ashley Fenstermacher; Simoni-Wastila, Linda (2008)Background. Recent studies have suggested there is an increased risk of cardiovascular (CV) events with some or all of the more Cox-II selective NSAIDs. One theory for this increased risk proposes that a shift in the balance between prostacyclin, an antithrombotic vasodilator that is reduced by Cox-II inhibition, and thromboxane A2, a prothrombotic vasoconstrictor that is reduced by Cox-I inhibition will theoretically increase the risk for CV and thrombotic events. This study attempts to specifically evaluate this theory by examining the association between CV events and the relative Cox-II to Cox-I selectivity of NSAIDs. Methods. Using 2000-2001 MarketScan claims data, cross-sectional and longitudinal analyses were performed. Univariate and bivariate analyses were performed to describe and compare new, adult users of NSAIDs. Propensity score matching was used to create a subset of these users, which was balanced across numerous covariates. Finally, multivariate, time to event analyses were performed using the matched sample to test the association between relative Cox-II to Cox-I selectivity ratio and possible adverse cardiovascular events. Results. Patients who were older, male, and had higher baseline cardiovascular risk were significantly more likely to receive a higher Cox-II selective drug than a lower Cox-II selective drug. In the propensity score matched sample, adjusted for confounders, the hazard of CV event was not significantly associated with increasing Cox-II selectivity ratios. Conclusion. This study shows that patients with an increased baseline risk of CV events are significantly more likely to receive a higher Cox-II selective NSAID. After controlling for these baseline differences, no significant association was found between selectivity ratios and CV events. Therefore, using Cox-II selectivity ratios to rank order NSAIDs in terms of risk of CV events is not appropriate and practitioners should not rely on selectivity ratios in making prescribing decisions. Additional studies should evaluate other potential mechanisms contributing to the CV risk of NSAIDs, while further study, in a larger sample and for a longer duration, should be performed to confirm the absence of an association between CV adverse events and Cox-II selectivity ratios.
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Functional variants in the sucrase-isomaltase gene associate with increased risk of irritable bowel syndromeHenström, M.; Diekmann, L.; Bonfiglio, F. (BMJ Publishing Group, 2018)Objective IBS is a common gut disorder of uncertain pathogenesis. Among other factors, genetics and certain foods are proposed to contribute. Congenital sucrase-isomaltase deficiency (CSID) is a rare genetic form of disaccharide malabsorption characterised by diarrhoea, abdominal pain and bloating, which are features common to IBS. We tested sucrase-isomaltase (SI) gene variants for their potential relevance in IBS. Design We sequenced SI exons in seven familial cases, and screened four CSID mutations (p.Val557Gly, p.Gly1073Asp, p.Arg1124Ter and p.Phe1745Cys) and a common SI coding polymorphism (p.Val15Phe) in a multicentre cohort of 1887 cases and controls. We studied the effect of the 15Val to 15Phe substitution on SI function in vitro. We analysed p.Val15Phe genotype in relation to IBS status, stool frequency and faecal microbiota composition in 250 individuals from the general population. Results CSID mutations were more common in patients than asymptomatic controls (p=0.074; OR=1.84) and Exome Aggregation Consortium reference sequenced individuals (p=0.020; OR=1.57). 15Phe was detected in 6/7 sequenced familial cases, and increased IBS risk in case-control and population-based cohorts, with best evidence for diarrhoea phenotypes (combined p=0.00012; OR=1.36). In the population-based sample, 15Phe allele dosage correlated with stool frequency (p=0.026) and Parabacteroides faecal microbiota abundance (p=0.0024). The SI protein with 15Phe exhibited 35% reduced enzymatic activity in vitro compared with 15Val (p<0.05). Conclusions SI gene variants coding for disaccharidases with defective or reduced enzymatic activity predispose to IBS. This may help the identification of individuals at risk, and contribute to personalising treatment options in a subset of patients. Copyright Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.