Respiratory syncytial virus (RSV) readily infects and reinfects during infancy and throughout life, despite maternal antibodies and immunity from prior infection and without the need for significant antigenic change. RSV has two neutralization antigens, the F and G virion glycoproteins. G is expressed in both membrane-bound (mG) and secreted (sG) forms. We investigated whether sG might act as a decoy for neutralizing antibodies by comparing the in vitro neutralization of wild-type (wt) RSV versus recombinant mG RSV expressing only mG. wt RSV indeed was less susceptible than mG RSV to monovalent G-specific and polyvalent RSV-specific antibodies, whereas susceptibility to F-specific antibodies was equivalent. This difference disappeared when the virus preparations were purified to remove sG. Thus, sG appears to function as a neutralization decoy. We evaluated this effect in vivo in mice by comparing the effects of passively transferred antibodies on the pulmonary replication of wt RSV versus mG RSV. Again, wt RSV was less sensitive than mG RSV to G-specific and RSV-specific antibodies; however, a similar difference was also observed with F-specific antibodies. This confirmed that sG helps wt RSV evade the antibodydependent restriction of replication but indicated that in mice, it is not acting primarily as a decoy for G-specific antibodies, perhaps because sG is produced in insufficient quantities in this poorly permissive animal. Rather, we found that the greater sensitivity of mG versus wt RSV to the antiviral effect of passively transferred RSV antibodies required the presence of inflammatory cells in the lung and was Fc␥ receptor dependent. Thus, sG helps RSV escape the antibody-dependent restriction of replication via effects as an antigen decoy and as a modulator of leukocytes bearing Fc␥ receptors.Human respiratory syncytial virus (RSV) is the leading viral agent of serious pediatric respiratory tract disease worldwide (10). Yearly infections and deaths due to RSV worldwide are estimated to be 64 million and 160,000, respectively (53). A striking feature of RSV is its ability to infect neonates and infants very early in life despite the presence of maternally derived virus-neutralizing serum antibodies. Indeed, the peak of serious RSV disease occurs at 2 months of age, a time in life when maternal antibodies protect infants against most other pathogens. Another striking characteristic of RSV is its ability to reinfect and cause disease throughout life, sometimes even during the same epidemic season, despite having only a single serotype (17,19,20,22; reviewed in reference 10). The ability of RSV to infect very early in life despite maternal antibodies and to reinfect throughout life despite immunity from prior infection accounts for much of its impact on human health.RSV has two major virion envelope proteins, the fusion F and major attachment G glycoproteins, which are the two viral neutralization antigens. The full-length RSV membranebound G protein (mG), which is anchored by a transmembrane domain near t...
An optimized repeated-fed-batch fermentation process for the synthesis of dihydroxyacetone (DHA) from glycerol utilizing Gluconobacter oxydans is presented. Cleaning, sterilization, and inoculation procedures could be reduced significantly compared to the conventional fed-batch process. A stringent requirement was that the product concentration was kept below a critical threshold level at all times in order to avoid irreversible product inhibition of the cells. On the basis of experimentally validated model calculations, a threshold value of about 60 kg x m(-3) DHA was obtained. The innovative bioreactor system consisted of a stirred tank reactor combined with a packed trickle-bed column. In the packed column, active cells could be retained by in situ immobilization on a hydrophilized Ralu-ring carrier material. Within 17 days, the productivity of the process could be increased by 75% to about 2.8 kg x m(-3) h(-1). However, it was observed that the maximum achievable productivity had not been reached yet.
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