While functionally distinct, these gene products collaborate to block the synthesis of new viral particles and to inhibit their release from the infected cell. However, some examples of the more well-characterized genes include 2′-5′-oligoadenylate synthase (OAS), RNAseL (RNASEL), interferon-stimulated gene 56 ( IFIT1), and Viperin (RSAD2). Only a small fraction of the known IFN-α/β-induced genes have been studied extensively, and many genes await functional analyses. Evolutionary predecessors of some of these genes can be traced as far back as fruit flies, and their importance in fighting viral infections is underscored by their conservation across the animal kingdom. Over 300 interferon-induced genes have been identified in humans and other species, and the majority of these genes are completely silent until activated by IFN-α/β signaling. The many genes induced by IFN-α/β evolved with a myriad of functions but with a common purpose: to block virus replication and spread to neighboring cells ( Sadler and Williams, 2008 ). IFN-α/β can be secreted locally and systemically in response to innate sensing of viral infections, and as such, triggers an immediate response both within infected cells as well as in neighboring uninfected cells. Farrar, in Reference Module in Biomedical Sciences, 2014 Interferon-Induced Antiviral Genes A key role for IFIT1 in negative-strand RNA viruses (VSV, Influenza) and positive-strand RNA viruses (WNV, MHV) except picornaviruses was reported ( Daffis et al., 2010 Habjan et al., 2013 Pichlmair et al., 2011). Binding of eIF4E to cap0 structures in lysates of IFN-primed cells is rather enhanced than reduced, suggesting additional mechanisms beyond eIF4E competition for 48S disruption ( Habjan et al., 2013). However, while in vitro competition experiments convincingly show that IFIT1 can compete with eIF4E for binding at completely unmethylated cap0 RNA, the out-competing of eIF4E from N7 methylated cap (cap0) structures is unclear. ![]() IFIT1 competes with eIF4E, the endogenous 5′-cap binding and translation factor, in the 48S initiation complex formation. Replacing the triphosphate with a 5′-cap, a 5′-monophosphate or 5′-OH diminishes the binding significantly ( Abbas et al., 2013). Unlike RIG-I, IFIT1 and IFIT5 preferentially bind to single-stranded RNA or to double-stranded RNA with a minimum three (IFIT5) or five (IFIT1)-nucleotide overhangs containing an uncapped triphosphate group at the 5′-end of RNA ( Abbas, Pichlmair, Gorna, Superti-Furga, & Nagar, 2013 Habjan et al., 2013 Kumar et al., 1994). Like RIG-I, productive binding of both IFIT1 and IFIT5 was shown to depend on the presence of cytosolic 5′-triphosphate RNA and is nonsequence specific. In humans, there are four well-characterized paralogues, IFIT1 (p56/ISG56), IFIT2 (p54/ISG54), IFIT3 (p60/ISG60), and IFIT5 (p58/ISG58). They are evolutionarily conserved from fish to mammals. They represent innate immune effector molecules that confer antiviral defense downstream of type I IFN through disruption of the host translation initiation machinery ( Daffis et al., 2010 Pichlmair et al., 2011 ). Interferon-induced proteins with tetratricopeptide repeats (IFITs) are among the most abundantly expressed proteins of the group of interferon-stimulated genes (ISGs). Hartmann, in Advances in Immunology, 2017 7.4 IFIT1 and IFIT5 iFIT has been embroiled in several lawsuits over the past couple of years, being sued by and countersuing Peloton.G. ![]() Previous trips to court haven’t sunk the company, either. It had even expanded its portfolio, acquiring Sweat and 29029. In the fiscal year 2021, iFIT generated $1.7 billion in revenue, a major bump from the previous year, when the brand garnered $851.7 million. Just a few short months ago, when the company had filed for an IPO, things were looking up for iFIT - or at least they appeared to be. Like Peloton - whose struggles were partially due to a drop in demand for at-home fitness - iFIT is reportedly hemorrhaging money.The lawsuit comes shortly after the company canceled an IPO which could have raised around $650 million.The reported $300 million lawsuit could cause the company to file for bankruptcy. ![]() One of the company’s lenders, Pamplona Capital Management, filed a lawsuit against iFIT over an agreement iFIT made with a China-based manufacturer, according to The New York Post. Peloton isn’t the only at-home fitness company facing major financial dilemmas - so is rival iFIT Health and Fitness, which sells NordicTrack products.
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