Human blood lymphocytes stimulated with nonviral antigens in vitro produce an antiviral substance with the biological and biochemical characteristics of interferon. The induced response was specific for cells obtained from immune donors. Cells from nonimmune donors did not produce interferon on exposure to these substances. The quantity of interferon produced by antigen stimulation was related to concentration of antigen over a relatively narrow range; with higher concentrations induction was decreased. Interferon production was maximum during days 4 to 7 in culture. In contrast, phytohemagglutinin-induced interferon was primarily produced during the first 4 days in culture.

Inhibitory effect of heparin on herpes simplex virus. J. Bacteriol. 87:1060-1066. 1964.-A substance inhibitory to herpes simplex virus was observed during experiments with leukocyte cultures. The component in the cultures responsible for this inhibition was identified as heparin. The minimal inhibitory concentration required to inhibit 30 to 300 TCD5 of the virus in human amnion tissue 1060

A positive correlation was found between genetic predisposition to diabetes in the mouse and susceptibility to group B Coxsackie virus in this host. Male mice of the inbred strain C57BL/Ks and the following genetic variants were used; mice homozygous for the autosomal recessive gene for diabetes (db/db), the phenotypically normal heterozygous (db/+), and the normal mice which lacked the diabetic gene (+/+). The mortality response of the +/+ mice to intraperitoneal inoculation with Coxsackie virus B4 differed from the response of the two genetic variants (db/db and db/+) derived from this strain. The db/+ variant was more susceptible to Coxsackie virus B4 than the parental background strain (+/+). The db/db variant was more susceptible than either of the other genotypes. Pathological findings of the pancreas of the three genotypes during the acute stage of infection closely paralleled the genotypically dependent susceptibility of the host.

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Infection of herpes simplex virus type-2-transformed hamster tumor cells with adeno-associated virus type 1 before inoculation into hamsters specifically delayed the appearance of palpable tumors and increased the survival time of the animals. The data indicated that a defective virus of humans can influence cancer expression by a virus-transformed cell.

Adult male mice were made hypercholesterolemic by a diet high in cholesterol, cholic acid, animal fat, and sucrose. After three months on this diet, animals were infected with 5 X 10(9) plaque-forming units of coxsackievirus B5. Control groups consisted of uninfected hypercholesterolemic mice and infected mice maintained on a standard laboratory diet. Infection in the hypercholesterolemic animals was associated with leukopenia, severe fatty metamorphosis and focal necrosis in the liver, cholelithiasis, ileus, cardiomyolysis, and lack of inflammatory response. These mice died within seven to 14 days. Uninfected hypercholesterolemic animals had lesser degrees of fatty liver and cholelithiasis, and all survived. Infected mice maintained on a standard diet also survived. Titers of virus in representative tissues were lower in the hypercholesterolemic than in the normal mice, an indication that replication of virus was not solely responsible for the lethal outcome of the infections. These experiments demonstrate that hypercholesterolemia may alter host defenses against group B coxsackievirus in the mouse.

In view of our recent findings that heparin had an inhibitory effect on herpes simplex virus ( 1 ) , various synthetic and other biological polyanions were investigated for similar activity. To ascertain possible relationships of such compounds to this inhibitory effect, the following characteristics were studied: nature, size and branching of the polyanionic molecule; nature and amount of negative groups; and relative importance of the polysaccharide portion. The biological preparations, hyaluronic acid, keratosulfate, chondroitin sulfates A, B, and C were also tested because of their possible role as a host defense mechanism in viral infection.Matmkls and methods. Virus. A laboratory strain of herpes simplex virus (Rodanus) which had undergone multiple passages in eggs and primary human amnion tissue cultures, was employed for all experiments. (Seven other strains of this virus, including 4 recent clinical isolates, had previously been found to be similarly inhibited by heparin.)Tissue culture and media. Primary humari amnion cultures were prepared and maintained with bovine amniotic fluid niedia ( 2 ). Substances tested: A. Biological polyanions 1. Heparin. Panheparin solution (Abbott #2945--Chicago, Ill.), 20,000 USP units/ml, 100 unitsAmg, containing no preszrvatives. (Five other heparin preparations from 3 different sites of pork and beef material, obdined from 3 different companies, had previously bee8 found to exhibit a similay inhibitory 'effect on herpes sfrriplex virus.) 2. Keratosulfate (M VI 52 IV) t 3. Chondroitin sulfate A (M VII 34 111) t 4. Chondroitin sulfate B (M VII 33 AI)t 5. Chondroitin sulfate C (M V 98 1I)t 6. Hyaluronic acid-sodium salt from human umbilical cord. (a) from Sigma Chemical Co., (b) from Dr. E. Balazs, Retina Foundation, Boston.