The newly emerged Middle East respiratory syndrome coronavirus (MERS-CoV) has circulated in bats for a substantial time, before making the species leap to humans, according to research published in BioMed Central's open access publication Virology Journal. By analysing the genome of various bat species, scientists show that bat DPP4 genes have adapted significantly as they evolved, suggesting a long-term arms race between the bat and the virus.

Previous work has shown that MERS-CoV uses the DPP4 receptor to enter the cell and it is well known that viruses can leave evolutionary footprints in receptor-encoding genes of hosts and their binding domains during long battles with the hosts. Jie Cui, colleagues from the University of Sydney and collaborators from the Duke-NUS Graduate Medical School and CSIRO analysed the sequence of DPP4 from seven bat genomes. They then compared the findings to those of a range of non-bat mammalian species. They go on to identify three residues in bat DPP4 under positive selection that directly interact with the viral surface glycoprotein.

Their findings show more pressure on the bat genes than in other species, with mutations occurring at a faster rate, suggesting that the newly emerged MERS-CoV not only has a bat origin, but also evolved over an extended time period in bat populations before making the leap to infect humans. Further research will be needed to understand the transmission route by collecting more bat MERS-CoVs.

Jie Cui, lead author on the paper, says: "Our analysis suggests that an evolutionary lineage leading to the current MERS-CoV co-evolved with bat hosts for an extended time period, eventually jumping species boundaries to infect humans, perhaps through an intermediate host."

ConclusionSubjects with asymptomatic BHR may experience fewer symptoms in daily life because they have less small airway dysfunction. (Source: Allergy)

Despite aggressive fixed-dose (FD) combination therapy with inhaled glucocorticosteroids (ICS) and long acting beta₂-adrenoceptor agonists (LABA), many patients with asthma remain suboptimally controlled, based on the need for rescue therapy and rates of severe exacerbations. The strategy of adjustable maintenance dosing (AMD) involves adjustment of the maintenance dose, (using a single combination [budesonide/formoterol] inhaler, Symbicort^®) in response to variability of asthma control over time. The AMD strategy, like the FD approach, involves the use of a short-acting ₂-adrenoceptor agonist (SABA) for rapid relief of bronchospasm. The dose-response characteristics of budesonide/formoterol make the AMD strategy a feasible option that cannot be exploited with the combination of salmeterol/fluticasone propionate (Advair^®). Several studies suggest that the AMD strategy is superior to a FD approach in terms of overall asthma control. Budesonide/formoterol in a single inhaler is as effective as albuterol (salbutamol) for relief of acute asthma episodes, a feature that makes it possible to use this combination for both maintenance and reliever therapy without the need for the use of a SABA. The single-inhaler strategy has been shown to be safe and more efficacious than FD therapy. In particular, the COSMOS study has demonstrated that exacerbation burden is reduced more effectively when the combination (budesonide/formoterol) single inhaler is used for both maintenance and relief compared with FD therapy with salmeterol/fluticasone and albuterol for rescue in patients with moderate-to-severe asthma. These findings suggest that we will have to reconsider our definition of reliever therapy for patients that require long-term therapy with combination ICS and LABA. The concept of single-inhaler therapy represents a paradigm shift in asthma management that has been validated in several large studies involving thousands of patients. The single-inhaler strategy represents one of the most significant advances in asthma management in many years, and one that appears ideal for adoption in primary care.