Monoclonal antibodies that bind to domain III of dengue virus E glycoprotein are the most efficient blockers of virus adsorption to Vero cells.

The specific mechanisms by which antibodies neutralize flavivirus infectivity are not completely understood. To study these mechanisms in more detail, we analyzed the ability of a well-defined set of anti-dengue (DEN) virus E-glycoprotein-specific monoclonal antibodies (MAbs) to block virus adsorption to Vero cells. In contrast to previous studies, the binding sites of these MAbs were localized to one of three structural domains (I, II, and III) in the E glycoprotein. The results indicate that most MAbs that neutralize virus infectivity do so, at least in part, by the blocking of virus adsorption. However, MAbs specific for domain III were the strongest blockers of virus adsorption. These results extend our understanding of the structure-function relationships in the E glycoprotein of DEN virus and provide the first direct evidence that domain III encodes the primary flavivirus receptor-binding motif.

Evolutionary reversals during viral adaptation to alternating hosts.

Experimental adaptation of the bacteriophage phiX174 to a Salmonella host depressed its ability to grow on the traditional Escherichia host, whereas adaptation to Escherichia did not appreciably affect growth on Salmonella. Continued host switching consistently exhibited this pattern. Growth inhibition on Escherichia resulted from two to three substitutions in the major capsid gene. When these phages were forced to grow again on Escherichia, fitness recovery occurred predominantly by reversions at these same sites, rather than by second-site compensatory changes, the more frequently observed mechanism in most microbial systems. The affected residues lie on the virion surface and they alter attachment efficiency, yet they occur in a region distinct from a putative binding region previously identified from X-ray crystallography. These residues not only experienced high rates of evolution in our experiments, but also exhibited high levels of radical amino acid variation among phiX174 and its known relatives, consistent with a history of adaptation involving these sites.

Within- and between-generation effects of temperature on early fecundity of Drosophila melanogaster.

We used a repeated-measures, four-factor experimental design to determine how the fecundity of Drosophila melanogaster during the first 5 days of adult life was influenced by paternal, maternal, developmental and laying temperature, with two different temperature levels (18 degrees C vs. 25 degrees C) per factor. Laying temperature had by far the largest effect on fecundity and accounted for 79 per cent of the variance in overall fecundity: flies laying at 25 degrees C began laying eggs about a day earlier and had much higher daily fecundities than did those laying at 18 degrees C. Developmental temperature had no significant effect either on overall fecundity or on the pattern of daily egg production. Dam temperature had a slight effect on the pattern of daily egg production, but not on overall fecundity. In contrast, sire temperature slightly influenced both overall fecundity and the pattern of daily egg production. Our results demonstrate that early fecundity is extraordinarily sensitive to laying temperature (360 per cent increase if laying at 25 degrees C vs. at 18 degrees C), but is relatively well buffered against developmental and cross-generational effects (maximum effect only 7 per cent, for sire temperature).