The molecular basis of antigenic drift was determined for the hemagglutinin (HA) of human influenza A/H3N2 virus. From 1968 to 2003, antigenic change was caused mainly by single amino acid substitutions, which occurred at only seven positions in HA immediately adjacent to the receptor binding site. Most of these substitutions were involved in antigenic change more than once. Equivalent positions were responsible for the recent antigenic changes of influenza B and A/H1N1 viruses. Substitution of a single amino acid at one of these positions substantially changed the virus-specific antibody response in infected ferrets. These findings have potentially far-reaching consequences for understanding the evolutionary mechanisms that govern influenza viruses.

Respiratory tract infections can be caused by a wide variety of viruses. Airborne transmission via droplets and aerosols enables some of these viruses to spread efficiently among humans, causing outbreaks that are difficult to control. Many outbreaks have been investigated retrospectively to study the possible routes of inter-human virus transmission. The results of these studies are often inconclusive and at the same time data from controlled experiments is sparse. Therefore, fundamental knowledge on transmission routes that could be used to improve intervention strategies is still missing. We here present an overview of the available data from experimental and observational studies on the transmission routes of respiratory viruses between humans, identify knowledge gaps, and discuss how the available knowledge is currently implemented in isolation guidelines in health care settings.

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In 2012, a previously unknown human coronavirus (CoV), now named Middle East respiratory syndrome CoV (MERS-CoV), was isolated from the sputum of a 60-year-old man in Saudi Arabia who presented with acute pneumonia with a fatal outcome (1, 2). To date, several infection clusters have been reported over a 1-year period, with around 50% of the reported human cases being fatal (3). MERS-CoV represents a novel betacoronavirus species, with the closest known relatives being clade 2c bat CoVs detected in bats (4, 5). Although MERS-CoV replicates in cells of bats, pigs, and (non-)human primates (6), its ability to infect some animal species may be restricted given the fact that hamsters were shown to resist MERS-CoV infection (7). However, these host factors have not been well characterized.We recently identified dipeptidyl peptidase 4 (DPP4) as a functional MERS-CoV receptor in human and bat cells (8). To further analyze DPP4 usage by MERS-CoV in vivo, ferrets (Mustela putorius furo; n ϭ 4), known to be susceptible to several respiratory viruses, including severe acute respiratory syndrome CoV (SARS- staining or S1-Fc binding on ferret kidney cells incubated with either goat anti-DPP4 polyclonal serum or S1-Fc (5 g/ml) followed by incubation with fluorescein isothiocyanate (FITC)-labeled rabbit anti-goat IgG antibody or FITC-labeled goat anti-human IgG, respectively (red lines). Normal goat serum, feline CoV S1-Fc protein (blue lines), and mock-incubated cells (gray shading) were used as controls. (E) MERS-CoV infection of primary ferret kidney cells transfected with a control plasmid or with a plasmid encoding hDPP4, stained for DPP4, S1 binding, and MERS-CoV as described previously (13).