The genetic diversity of representative members of the Lyssavirus genus (rabies and rabies-related viruses) was evaluated using the gene encoding the transmembrane glycoprotein involved in the virus-host interaction, immunogenicity, and pathogenicity. Phylogenetic analysis distinguished seven genotypes, which could be divided into two major phylogroups having the highest bootstrap values. Phylogroup I comprises the worldwide genotype 1 (classic Rabies virus), the European bat lyssavirus (EBL) genotypes 5 (EBL1) and 6 (EBL2), the African genotype 4 (Duvenhage virus), and the Australian bat lyssavirus genotype 7. Phylogroup II comprises the divergent African genotypes 2 (Lagos bat virus) and 3 (Mokola virus). We studied immunogenic and pathogenic properties to investigate the biological significance of this phylogenetic grouping. Viruses from phylogroup I (Rabies virus and EBL1) were found to be pathogenic for mice when injected by the intracerebral or the intramuscular route, whereas viruses from phylogroup II (Mokola and Lagos bat viruses) were only pathogenic by the intracerebral route. We showed that the glycoprotein R333 residue essential for virulence was naturally replaced by a D333 in the phylogroup II viruses, likely resulting in their attenuated pathogenicity. Moreover, cross-neutralization distinguished the same phylogroups. Within each phylogroup, the amino acid sequence of the glycoprotein ectodomain was at least 74% identical, and antiglycoprotein virus-neutralizing antibodies displayed cross-neutralization. Between phylogroups, the identity was less than 64.5% and the cross-neutralization was absent, explaining why the classical rabies vaccines (phylogroup I) cannot protect against lyssaviruses from phylogroup II. Our tree-axial analysis divided lyssaviruses into two phylogroups that more closely reflect their biological characteristics than previous serotypes and genotypes.

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This study compared a panel of 10 enzyme-linked immunosorbent assays (ELISAs) for the serodiagnosis of Mediterranean visceral leishmaniasis (MVL). The ELISAs were based on either one of the following Leishmania antigens: crude soluble Leishmania antigens (SLAs), recombinant (r) antigens (namely: rgp63, rK39, gene B protein, r H2A and r H2B histones proteins, rLACK, rPSA-2, r P20) and purified lipophosphoglycan. Most of the test antigens showed good performance (sensitivity > 85%, specificity > 80%). rK39 and SLA-based ELISA gave the best results in terms of sensitivity (100%) and predictive value of the negative (100%). The best specificity (97%) and the best predictive value of the positive (92%) were obtained with rK39. These results show that several Leishmania antigens are suitable to design a diagnostic ELISA of MVL. However, recombinant proteins add little to the classic crude SLA, which still represents a very good and less costly alternative.