Altered Patterns of Gene Expression Underlying the Enhanced Immunogenicity of Radiation-Attenuated Schistosomes

Schistosoma mansoni is a blood-dwelling parasitic worm that causes schistosomiasis in humans throughout Africa and parts of South America. A vaccine would enhance attempts to control and eradicate the disease that currently relies on treatment with a single drug. Although a manufactured vaccine has yet to generate high levels of protection, this can be achieved with infective parasite larvae that have been disabled by exposure to radiation. How these weakened parasites are able to induce protective immunity when normal parasites do not, is the question addressed by our experiments. We have used a technique of gene expression profiling to compare the patterns in normal and disabled parasites, over the period when they would trigger an immune response in the host. We found that only a handful of genes were differentially expressed, all of them diminished in the disabled parasite. However, a more sensitive technique to examine groups of genes revealed that those involved in nervous system and muscle function were depressed in the disabled parasites. We suggest that reduced mobility of these larvae permits them longer contact with the immune system, thus enabling a strong protective immune response to develop

Virus-like particle capsid proteins encoded by different L double-stranded RNAs of Saccharomyces cerevisiae: their roles in maintenance of M double-stranded killer plasmids.

The plasmid determinants of killer phenotypes in type K1 and K2 killer yeast cells are the 1.9-kilobase (kb) M1 and 1.7-kb M2 double-stranded RNAs (dsRNAs), respectively. These are dependent for their maintenance and encapsidation, in Saccharomyces cerevisiae virus ScV-M1 or ScV-M2 virus-like particles, on the capsid provided by one of a group of moderately related 4.7-kb dsRNAs called LA. The L1A and L2A dsRNAs found in naturally isolated K1 and K2 killers encode 88-kilodalton VL1A-P1 and 86-kilodalton VL2A-P1 capsids, respectively. These are competent for encapsidating homologous LA dsRNAs as well as M dsRNAs. Most strains of S. cerevisiae, including killers, contain one of a second group of closely related 4.7-kb dsRNAs called LBC. These encode their own 82-kilodalton capsid protein, VLBC-P1, which, at least in strains containing only LBC, encapsidates homologous dsRNA in ScV-LBC virus-like particles. In a K1 killer strain containing both L1A and LBC, ScV-M1 particles contain only VL1A-P1. In such strains it is probable that each virus-like particle contains a single capsid type and that each L dsRNA is encapsidated by a homologous capsid