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Our data provide strong evidence that HBV viral particles themselves can readily inhibit host innate immune responses upon virion/cell interactions, and may explain, at least partially, the "stealthy" character of HBV.

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Background and aims. Liver macrophages can be both involved in pathogen clearance and/or pathogenesis. To get further insight on their role during chronic hepatitis B virus (HBV) infections, our aim was to phenotypically and functionally characterize in vivo and ex vivo the interplay between HBV, primary human liver macrophages (PLM) and primary blood monocytes differentiated into pro-inflammatory or anti-inflammatory macrophages (M1-MDM or M2-MDM, respectively).Results. We evidenced the presence of HBc protein within macrophages in liver biopsies from HBV-infected patients and higher levels of anti-inflammatory macrophages markers, compared to non-infected ones. Ex vivo exposure of naive PLM to HBV led to a reduced secretion of proinflammatory cytokines. Upon exposure to HBV or HBV-producing cells during differentiation and activation, M1-MDM secreted less IL-6 and IL-1β, whereas M2-MDM secreted more IL-10 when exposed to HBV during activation. Finally, cytokines produced by M1-MDM, but not those produced by HBV-exposed M1-MDM, decreased HBV infection of hepatocytes.Conclusions. Altogether, our data strongly suggest that HBV modulates liver macrophage functions to favour its establishment. Lay summary: HBV modulates liver macrophages function in order to favour its establishment and likely its maintenance. It impairs the production of the antiviral cytokine IL-1β while promoting that of IL-10 in the microenvironment. This phenotype can be recapitulated in naive liver macrophages or monocytes-derived-macrophages ex vivo by short exposure to the virus or cells replicating the virus, thus suggesting an "easy to implement" mechanism of inhibition.

There is growing evidence that virus particles contain host cell proteins. These proteins may provide viruses with means to evade the immune system or with mechanisms for cell entry and release. A proteomic analysis carried out on highly purified HCV J6/JFH virions identified the heat shock cognate protein 70 (HSC70) as part of the viral particles. These results were further validated by immunogold electron microscopy. The HSC70 interaction HPD motif was found present on the E2 envelope of the J6/JFH strain, as well as in over 50% of genotype 2 clinical HCV isolates. In addition, HSC70 was found associated with viral particles from an HCV genotype 2a-infected patient. Pre-incubation of HCV particles with anti-HSC70 antibodies decreased viral infectivity. Within infected cells, colocalization of HSC70 with the HCV core and E2 proteins was observed around lipid droplets. Reduction of HSC70 expression by an RNAi approach decreased the volume of lipid droplets as well as viral release without affecting HCV replication levels. Conclusion These results suggest that HSC70 modulates HCV infectivity and lipid-droplet dependent virus release.

Two novel peptides that inhibit the intra-erythrocyte stage of Plasmodium falciparum in vitro were identified in the venom of the Trinidad chevron tarantula, Psalmopoeus cambridgei. Psalmopeotoxin I (PcFK1) is a 33-residue peptide and Psalmopeotoxin II (PcFK2) has 28-amino acid residues; both have three disulfide bridges and belong to the Inhibitor Cystine Knot superfamily. The cDNAs encoding both peptides were cloned, and nucleotide sequence analysis showed that the peptides are synthesized with typical signal peptides and pro-sequences that are cleaved at a basic doublet before secretion of the mature peptides. The IC(5O) of PcFK1 for inhibiting P. falciparum growth was 1.59+/-1.15 microM and that of PcFK2 was 1.15+/-0.95 microM. PcFK1 was adsorbed strongly to uninfected erythrocytes, but PcFK2 was not. Neither peptide has significant hemolytic activity at 10 microM. Electrophysiological recordings in isolated frog and mouse neuromuscular preparations revealed that the peptides (at up to 9.3 microM) do not affect neuromuscular transmission or quantal transmitter release. PcFK1 and PcFK2 do not affect the growth or viability of human epithelial cells, nor do they have any antifungal or antibacterial activity at 20 microM. Thus, PcFK1 and PcFK2 seem to interact specifically with infected erythrocytes. They could therefore be promising tools for antimalaria research and be the basis for the rational development of antimalarial drugs.

The antigenic complexity of three strains of Bacteroides gingivalis and four strains resembling B. gingivalis isolated from animals was analyzed and compared by crossed immunoelectrophoresis. Thirteen antigens of the human biotype were present in all human strains and six antigens of the animal biotype were present in all animal strains, indicating a marked serological homogeneity within each biotype. Four antigens cross-reacting between the human B. gingivalis and the animal strains were identified. This antigenic relatedness defined the serological homogeneity of the two biotypes within the species and allowed recognition of four species-specific antigens. Two antigens specific to the human strains and two antigens specific to the animal strains were identified, indicating that serotype-specific antigens can distinguish each biotype. It is thus proposed that the oral, black-pigmented asaccharolytic Bacteroides strains of animal origin be classified as catalase-positive variants of B. gingivalis. It is also proposed that two serotypes be recognized within the species B. gingivalis. Serotype 1 includes the catalase-negative human biotype, and serotype 2 includes the catalase-positive animal biotype.

The hepatitis C virus (HCV) infects hepatocytes after binding to heparan sulfate proteoglycans, in particular Syndecan-1, followed by recognition of the tetraspanin CD81 and other receptors. Heparan sulfate proteoglycans are found in a specific microenvironment coating the hepatocyte surface called the glycocalyx and are receptors for extracellular matrix proteins, cytokines, growth factors, lipoproteins, and infectious agents. We investigated the mutual influence of HCV infection on the glycocalyx and revealed new links between Syndecan-1 and CD81. Hepatocyte infection by HCV was inhibited after knocking down Syndecan-1 or Xylosyltransferase 2, a key enzyme of Syndecan-1 biosynthesis. Simultaneous knockdown of Syndecan-1 and CD81 strongly inhibited infection, suggesting their cooperative action. At early infection stages, Syndecan-1 and virions colocalized at the plasma membrane and were internalized in endosomes. Direct interactions between Syndecan-1 and CD81 were revealed in primary and transformed hepatocytes by immunoprecipitation and proximity ligation assays. Expression of Syndecan-1 and Xylosyltransferase 2 was altered within days post-infection, and the remaining Syndecan-1 pool colocalized poorly with CD81. The data indicate a profound reshuffling of the hepatocyte glycocalyx during HCV infection, possibly required for establishing optimal conditions of viral propagation.