Oseltamivir-Resistant Pandemic A/H1N1 Virus Is as Virulent as Its Wild-Type Counterpart in Mice and Ferrets

The neuraminidase inhibitor oseltamivir is currently used for treatment of patients infected with the pandemic A/H1N1 (pH1N1) influenza virus, although drug-resistant mutants can emerge rapidly and possibly be transmitted. We describe the characteristics of a pair of oseltamivir-resistant and oseltamivir-susceptible pH1N1 clinical isolates that differed by a single change (H274Y) in the neuraminidase protein. Viral fitness of pH1N1 isolates was assessed in vitro by determining replication kinetics in MDCK α2,6 cells and in vivo by performing experimental infections of BALB/c mice and ferrets. Despite slightly reduced propagation of the mutant isolate in vitro during the first 24 h, the wild-type (WT) and mutant resistant viruses induced similar maximum weight loss in mice and ferrets with an identical pyrexic response in ferrets (AUC of 233.9 and 233.2, P = 0.5156). Similarly, comparable titers were obtained for the WT and the mutant strains on days 1, 3, 6 and 9 post-infection in mouse lungs and on days 1–7 in ferret nasal washes. A more important perivascular (day 6) and pleural (days 6 and 12) inflammation was noted in the lungs of mice infected with the H274Y mutant, which correlated with increased pulmonary levels of IL-6 and KC. Such increased levels of IL-6 were also observed in lymph nodes of ferrets infected with the mutant strain. Furthermore, the H274Y mutant strain was transmitted to ferrets. In conclusion, viral fitness of the H274Y pH1N1 isolate is not substantially altered and has the potential to induce severe disease and to disseminate

Visual search for transparency and opacity: attentional guidance by cue combination?

A series of seven experiments explored search for opaque targets among transparent distractors or vice versa. Static stimuli produced very inefficient search. With moving items, search for an opaque target among transparent distractors was quite efficient while search for transparent targets was less efficient (Experiment 1). Transparent and opaque items differed from each other on the basis of motion cues, luminance cues, and figural cues (e.g., junction type). Motion cues were not sufficient to support efficient search (Experiments 2–5). Violations of the luminance rules of transparency disrupt search (Experiments 3 and 4). Experiment 5 shows that search becomes inefficient if X-junctions are removed. Experiments 6 and 7 show that efficient search survives if X-junctions are occluded. It appears that guidance of attention to an opaque target is guidance based on “cue combination” (M. S. Landy, L. T. Maloney, E. B. Johnston, & M. Young, 1995). Several cues must be present to produce a difference between opaque and transparent surfaces that is adequate to guide attention