Host shutoff is a common strategy used by viruses to repress cellular mRNA translation and concomitantly allow the efficient translation of viral mRNAs. Here we use RNA-sequencing and ribosome profiling to explore the mechanisms that are being utilized by the Influenza A virus (IAV) to induce host shutoff. We show that viral transcripts are not preferentially translated and instead the decline in cellular protein synthesis is mediated by viral takeover on the mRNA pool. Our measurements also uncover strong variability in the levels of cellular transcripts reduction, revealing that short transcripts are less affected by IAV. Interestingly, these mRNAs that are refractory to IAV infection are enriched in cell maintenance processes such as oxidative phosphorylation. Furthermore, we show that the continuous oxidative phosphorylation activity is important for viral propagation. Our results advance our understanding of IAV-induced shutoff, and suggest a mechanism that facilitates the translation of genes with important housekeeping functions.DOI: http://dx.doi.org/10.7554/eLife.18311.001

BackgroundDuring the 2009 H1N1 influenza epidemic, policy makers debated over whether, when, and how long to close schools. While closing schools could have reduced influenza transmission thereby preventing cases, deaths, and health care costs, it may also have incurred substantial costs from increased childcare needs and lost productivity by teachers and other school employees.MethodsA combination of agent-based and Monte Carlo economic simulation modeling was used to determine the cost-benefit of closing schools (vs. not closing schools) for different durations (range: 1 to 8 weeks) and symptomatic case incidence triggers (range: 1 to 30) for the state of Pennsylvania during the 2009 H1N1 epidemic. Different scenarios varied the basic reproductive rate (R0) from 1.2, 1.6, to 2.0 and used case-hospitalization and case-fatality rates from the 2009 epidemic. Additional analyses determined the cost per influenza case averted of implementing school closure.ResultsFor all scenarios explored, closing schools resulted in substantially higher net costs than not closing schools. For R0 = 1.2, 1.6, and 2.0 epidemics, closing schools for 8 weeks would have resulted in median net costs of $21.0 billion (95% Range: $8.0 - $45.3 billion). The median cost per influenza case averted would have been $14,185 ($5,423 - $30,565) for R0 = 1.2, $25,253 ($9,501 - $53,461) for R0 = 1.6, and $23,483 ($8,870 - $50,926) for R0 = 2.0.ConclusionsOur study suggests that closing schools during the 2009 H1N1 epidemic could have resulted in substantial costs to society as the potential costs of lost productivity and childcare could have far outweighed the cost savings in preventing influenza cases.

While studies have found influenza vaccination to be cost-effective in older adults (65 years or older), they have not looked at how the vaccine's economic value may vary with the timing of vaccine administration. We developed a set of computer simulation models to evaluate the economic impact of vaccinating older adults at different months. Our models delineated the costs and utility losses in delaying vaccination past October and suggest that policy makers and payors may consider structuring incentives (≤ $2.50 per patient) to vaccinate in October. Our results also suggest that vaccination is still cost-effective through the end of February.

Enterovirus 71 (EV71) is a growing public health concern, especially in Asia. A surge of EV71 cases in 2008 prompted authorities in China to go on national alert. While there is currently no treatment for EV71 infections, vaccines are under development. We developed a computer simulation model to determine the potential economic value of an EV71 vaccine for children (<5 years old) in China. Our results suggest that routine vaccination in China (EV71 infection incidence 0.04%) may be cost-effective when vaccine cost is $25 and efficacy ≥70% or cost is $10 and efficacy ≥ 50%. For populations with higher infection risk (≥ 0.4%), a $50 or $75 vaccine would be highly cost-effective even when vaccine efficacy is as low as 50%.