Pathogen factors and host factors in murine pulmonary blastomycosis

Factors related to pathogenesis were studied in a murine model of pulmonary fungal infection with strains of Blastomyces dermatitidis. Strain 26199V was 10⁵-fold more lethal in pulmonary challenge than strain GA-1. This relationship between the two strains also occurred after intraperitoneal challenge. Serial studies with lung cultures and histology of sacrificed animals after pulmonary challenge with similar doses, and challenge studies in mice of differing maturity, indicated GA-1 is impaired in initial replication in situ, although the two strains grow equally well in the presence of murine substrates in vitro. In vitro studies indicated the two strains were indistinguishable in most studies of biochemical and metabolic markers, and in studies with chemical and physical inhibitors. The exceptions were their morphologic appearance in the yeast phase, ability to hydrolyze esculin, and susceptibility to crystal violet dye and bile. The last finding and previous work suggested possible differences in lipid content; these were confirmed in studies which also included two other strains. Greater phospholipid and palmitic acid content were associated with greater virulence.     

Passive immunization in murine mucormycosis

Antibody raised in mice against mycelial homogenates of Rhizomucor pusillus was effective in passive immunization against pulmonary and disseminated mucormycosis (phycomycosis) in immunocompromised mice. Mice intranasally inoculated and infected with Rh. pusillus and treated with antisera had a statistically significant increased resistance to infection and a diminished secondary dissemination of viable fungal fragments. Histological examination of infected lung tissues showed that antibody treated animals were apparently able to degrade hyphal fragments.     

Cyclophilins Facilitate Dissociation of the Human Papillomavirus Type 16 Capsid Protein L1 from the L2/DNA Complex following Virus Entry

Human papillomaviruses (HPV) are composed of the major and minor capsid proteins, L1 and L2, that encapsidate a chromatinized, circular double-stranded DNA genome. At the outset of infection, the interaction of HPV type 16 (HPV16) (pseudo)virions with heparan sulfate proteoglycans triggers a conformational change in L2 that is facilitated by the host cell chaperone cyclophilin B (CyPB). This conformational change results in exposure of the L2 N terminus, which is required for infectious internalization. Following internalization, L2 facilitates egress of the viral genome from acidified endosomes, and the L2/DNA complex accumulates at PML nuclear bodies. We recently described a mutant virus that bypasses the requirement for cell surface CyPB but remains sensitive to cyclosporine for infection, indicating an additional role for CyP following endocytic uptake of virions. We now report that the L1 protein dissociates from the L2/DNA complex following infectious internalization. Inhibition and small interfering RNA (siRNA)-mediated knockdown of CyPs blocked dissociation of L1 from the L2/DNA complex. In vitro, purified CyPs facilitated the dissociation of L1 pentamers from recombinant HPV11 L1/L2 complexes in a pH-dependent manner. Furthermore, CyPs released L1 capsomeres from partially disassembled HPV16 pseudovirions at slightly acidic pH. Taken together, these data suggest that CyPs mediate the dissociation of HPV L1 and L2 capsid proteins following acidification of endocytic vesicles.