Antigenic variation and cytoadherence of PfEMP1 of Plasmodium falciparum infected erythrocyte from malaria patients

To approve a theoretical basis for the molecular pathogenesis of human cerebral malaria and treatment with prevention Methods The blood samples were collected from 24 patients with cerebral malaria, 143 with falciparum malaria, 34 with vivax malaria and 20 healthy controls from the endemic areas of Yunnan Province, China Using the sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS PAGE) technique, we determined the molecular mass (Mr) of these Plasmodium falciparum (P falciparum) erythrocyte membrane protein 1 (PfEMP1) molecules Results Our findings indicate that higher molecular mass (260?kDa-320?kDa) forms of PfEMP1 were expressed on parasitized erythrocyte (PE) from human cerebral malaria patients Compared with PfEMP1 expressed on PE from human cerebral malaria patients, the expression of PfEMP1 and Plasmodium vivax (P vivax) erythrocyte membrane protein 1 (PvEMP1) on PE from falciparum malaria patients and vivax malaria patients did not have multiple bands of PfEMP1 of ≥260?kDa, but had a PfEMP1 with molecular mass of 240?kDa and a PvEMP1 with molecular mass of 180?kDa band separately Healthy controls expressed an EMP of molecular mass of 140?kDa Conclusion Results confirm the antigenic variation of higher molecular mass of PfEMP1 whose molecular mass is equal to or exceeds 260?kDa-320?kDa on PE of patients with cerebral malaria Our results show that the binding of large antigenic variability PfEMP1 molecular mass of 260?kDa-320?kDa on PE from human cerebral malaria patients with diverse receptor molecules on the endothelial cell (EC) of the cerebral microvessels may be involved in the molecular pathogenesis of cerebral malaria

Evolutionary Implication of Outer Membrane Lipoprotein-Encoding Genes ompL1,lipL32 and lipL41 of Pathogenic Leptospira Species

Leptospirosis is recognized as the most widespread zoonosis with a global distribution. In this study, the antigenic variation in Leptospira interrogans and Leptospira borgpetersenii isolated from human urine and field rat kidney was preliminarily confirmed by microscopic agglutination test using monoclonal antibodies, and was further subjected to amplification and identification of outer membrane lipoproreins with structural gene variation. Sequence similarity analysis revealed that these protein sequences, namely OmpL1, LipL32 and LipL41, showed no more homologies to outer membrane lipoproteins of non-pathogenic Leptospira and other closely related Spirochetes, but showed a strong identity within L. interrogans, suggesting intra-specific phylogenetic lineages that might be originated from a common pathogenic leptospiral origin. Moreover, the ompL1 gene showed more antigenic variation than lipL32 and lipL41 due to less conservation in secondary structural evolution within closely related species. Phylogenetically, ompL1 and lipL4l of these strains gave a considerable proximity to L. weilii and L. santaro- sai. The ompI,1 gene of L. interrogans clustered distinctly from other pathogenic and non-pathogenic leptospiral species. The diversity of ompL genes has been an- alyzed and it envisaged that sequence-specific variations at antigenic determinant sites would result in slow evolutionary changes along with new serovar origination within closely related species. Thus, a crucial work on effective recombinant vaccine development and engineered antibodies will hopefully meet to solve the therapeutic challenges.

Epigenetic regulations in immune evasion of the deadliest malaria parasite Plasmodium falciparum

Both eukaryotic and prokaryotic pathogens infect the host stably via an immune evasion mecha- nism termed mutually exclusive expression. Nowadays, little is known about this epigenetic mechanism, largely limiting the understanding of pathogenesis of many bacterial, fungal and protozoan pathogens and therefore the development of novel drugs and vaccines. In the most severe malaria parasite, Plasrnodiurn falciparum, there is a major virulence gene family termed vat, by which the variant antigen PfEMP1 is encoded and expressed on the surface of parasite-infected erythrocytes. Each parasite carries about 60 anti- genically various vat genes, however, only one of which is expressed at a given time during infection. P. falciparum expresses PfEMP1s in this clonally variant manner to bind to different human endothelial re- ceptors, allowing the infected erythrocytes to sequester in tissues to escape the host＇s immune response in- cluding spleen killing and humoral immunity. At present, the mechanism of mutually exclusive expression of the var gene family remains largely unknown, even though there is increasing evidence suggesting im- portant roles of the epigenetic regulation involved in vat gene expression. In addition, epigenetic factors were also found in association with transcriptional regulation of other antigenic variant gene families in P. falciparum. In this paper, we review the current understanding of epigenetic regulations of P. falcipa- rum virulence genes with particular views toward the design of novel vaccines, drugs, and diagnosis to ma- laria.

Automated recommendation of the seasonal influenza vaccine strain with PREDAC

Vaccination is currently the most effective way to protect against influenza viruses.This study presents PREDAC(PRE-Dict Antigenic Cluster),a sequence-based computational method to model antigenic clusters of influenza viruses.PREDAC could improve vaccine recommendations for influenza viruses and has been used to support the influenza vaccine strain recommendations at the Chinese National Influenza Center.Moreover,a PREDAC server which includes tools for the prediction of antigenic variants and antigenic clusters of both influenza A and B viruses was built and made publicly available at http://www.computationalbiology.cn/home/.PREDAC could not only facilitate systematic studies of the antigenic evolution of influenza viruses but also provide user-friendly tools for vaccine strain recommendations for influenza viruses.