The effect of Dextransulfate 500 on the pathogenesis of herpes simplex virus infections in weanling mice

Summary Intraperitoneal (i.p.) injection of Dextran Sulfate (D.S.) 500 during a limited period of time influences the course of herpes simplex-virus-infections. D.S.500 was found to reduce the resistance of mice for some herpes simplex-virus strains (Len, L3-2s, Haase) if given between 16 hours before and 2 hours after i.p. infection. The decrease of resistance could be correlated with an increase of the virus content of liver, spleen, brain and spinal cord. Injection of herpes simplex-virus-specific immune serum counteracted the effect of D.S.500 on the course of infections. Conversely, D.S.500 increased the resistance of mice to another group of herpes simplex-viruses (strains D-316, Thea, DD), if given 3 to 8 hours before infection.These effects are ascribed to a special interaction of D.S.500 with macrophages and probably other virus-susceptible cells of the peritoneal cavity and elsewhere with a resulting counteraction to the virus infection.With 2 FiguresIn part presented at the 76th Ordinary meeting of the Society for General Microbiology at the University of Cambridge, April 5–8, 1976.In partial fulfilment of the requirements for the MD degree.     

Role of bacterial products in periodontitis: immune response in gnotobiotic rats monoinfected with Eikenella corrodens.

The development of humoral and cell-mediated immune responses to Eikenella corrodens (a bacterium that causes periodontal lesions in gnotobiotic rats) was measured and compared with the rate of appearance of macroscopic lesions. A possible inverse relationship was found. A strong cell-mediated immune response, as measured by skin reactivity and lymphocyte mitogenesis, occurred between 4 and 6 weeks after infection and subsided soon thereafter to a low response level. Humoral antibodies to endotoxin from E. corrodens could not be detected at any time. The disease developed only after the cell-mediated immune response diminished, thus suggesting that lack of an efficient immune response may permit the development of the disease. This is seemingly in contradiction to the assumption that tissue destruction in such cases is caused by the immune response and its products. We are inclined to believe, based on our findings reported here, that the lack of immune responsiveness to the bacterium and/or its products is the major causative factor in the development of periodontitis. At the same time, we wish to emphasize that occurrence of both phenomena during the long development of periodontal disease is possible.     

Pasteurella multocida in scavenging family chickens and ducks: carrier status, age susceptibility and transmission between species.

Pasteurella multocida causes fowl cholera, a highly contagious and severe disease in chickens and water fowls. The disease is not well described in less intensive production systems, including scavenging family poultry production in developing countries. P. multocida was isolated from 25.9% of healthy-looking ducks and 6.2% of chickens from free-range family poultry farms and at slaughter slabs at market. On experimental infection with 1.2 to 2.0 x 10(8) organisms of the P. multocida type strain (NCTC 10322(T)), 12-week-old chickens expressed fowl cholera clinical signs significantly more times (372 signs) than those of 4-week-old, 8-week-old and 16-week-old chickens (173, 272 and 187 signs) and more signs were severe. In family ducks the 8-week-old birds expressed clinical signs significantly more times (188 signs) than those of the other age groups (117, 80, and 83 signs, respectively) and severe signs were more frequent. P. multocida transmitted from seeder birds (n=12) to sentinel birds (n=30), which developed clinical signs, and in some cases lesions of fowl cholera allowed bacterial re-isolation, whether infected ducks served as seeders for chickens or chickens served as seeder for ducks. This study has documented the occurrence of P. multocida among healthy-appearing family poultry in a tropical setting, and demonstrated that age susceptibility is highest in 12-week-old family chickens and 8-week-old family ducks when challenged with a low-virulent strain of P. multocida. It has further demonstrated that cross-transmission of fowl cholera may happen between family ducks and chickens, and vice versa.     

Trypanosoma lewisi: Cell populations and antibody formation in riboflavin deficient rats

Summary The influence of riboflavin deficiency on severity and duration of parasitemia was studied in Trypanosoma lewisi infected rats.The host dietary groups were: (1) complete or full complement; (2) riboflavin-deficient, and (3) pair-fed or calorically restricted. In all dietary groups, trypomastigotes appeared in peripheral tail blood of all inoculated rats after 7-day incubation periods. Riboflavin-deficient rats and pair-fed controls rats showed greater numbers of parasites than control-diet rats throughout the infection. The maximum parasitemia was on day 14 in control-diet rats; day 16 in riboflavin-deficient rats, and day 14 in pair-fed control rats. Parasitemia in riboflavin-deficient animals lasted 4 or more days longer than in the other two dietary groups.The average coefficients of variation in body length of trypomastigotes indicated that the formation of the reproduction inhibiting antibody (ablastin) was delayed seven days in riboflavin-deficient animals as compared with that in pair-fed and normal control animals.     

Lung surfactant proteins (SP-A and SP-D) in non-adaptive host responses to infection

The lung surfactant proteins A and D (SP-A and SP-D) are collectins composed of C-type lectin domains attached to collagen regions. SP-A and SP-D are mainly found in the surfactant covering the pulmonary epithelial cells, but are also produced by cells lining the gastrointestinal tract. The main role of SP-A and SP-D is to interact directly with carbohydrate on the surface of microbial pathogens, thereby initiating a variety of effector mechanisms. This review focuses on the non-adaptive host responses of SP-A and SP-D to infection. Interaction of SP-A and SP-D with phagocytes is discussed and the structure and function of the putative receptors for SP-A and SP-D is presented. SP-A and SP-D seem to be regulated in a way similar to acute-phase proteins in the course of inflammation and evidence for the involvement of SP-A and SP-D as immunomodulators as well as their role in clearing allergens and modulating effector mechanisms in allergic reactions is discussed.     

Purification and characterization of the reovirus cell attachment protein sigma 1

It has previously been shown that of all the soluble reovirus-specified proteins present in the infected cell lysate, protein sigma 1 alone possesses the capacity to bind to host cells (P.W.K. Lee, E.C. Hayes, and W.K. Joklik, 1981, Virology 108, 156-163). We found that sigma 1 from urea-disrupted reovirus particles was also capable of such specific binding. Reovirions were therefore used as a source of functional sigma 1. Accordingly, a simple procedure has been developed to purify sigma 1 by subjecting urea-disrupted reovirions to DEAE ion-exchange chromatography. Protein sigma 1 thus isolated was electrophoretically homogeneous and the recovery was estimated to be 50 to 60% of the theoretical yield. The purified protein presumably maintained its native conformation since it was recognized by a panel of monoclonal anti-sigma 1 antibodies previously isolated, and was capable of specifically binding to host cell receptors, agglutinating human erythrocytes and inducing neutralization and hemagglutination-inhibition antibodies. Subsequent chemical crosslinking studies revealed the presence of oligomeric (mostly dimeric) sigma 1 forms in the preparation. The amino acid composition of the purified sigma 1 was found to closely match that inferred from the S1 gene sequence. However, attempts to determine its amino-terminal sequence have not been successful. The p/ of the purified protein was determined to be 6.8. Circular dichroic measurements of the purified sigma 1 indicated that 54 and 19% of its residues were arranged in alpha-helical and beta-sheet secondary structures, respectively.