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Chlorite-oxidized amylose (COAM), polyinosinic-polycytidylic acid [poly(I:C)], and combinations of the two drugs were evaluated for their interferon-inducing properties and their ability to protect mice against rabies infection. Post-exposure administration of one or two doses (100 μg each) of poly(I:C) significantly protected mice against rabies infection. Pretreatment of mice with COAM 3 h before poly(I:C) stimulation resulted in an enhancement of the interferon response. However, the increased interferon titers were not reflected by increased protection against rabies infection over that achieved with poly(I:C) therapy alone. Therapy with COAM alone did not protect mice against rabies but, rather, was associated with enhanced mortality.

A murine model simulating human street rabies virus infection was used to evaluate the efficacy of polyriboinosinic-polyribocytidylic acid (poly I-poly C), three rabies vaccines, and combinations of these modes of therapy administered after exposure. One or two doses of 100 mug of poly I-poly C, injected into the same intramuscular site as the challenge virus, significantly reduced the mortality rate when therapy was initiated 3 hr after challenge; however, the same quantity of poly I-poly C injected into the opposite leg did not reduce the mortality rate. The muscle injected with poly I-poly C invariably contained four to eight times more interferon than a similar noninjected muscle from the same animal. Mice treated 3 hr after challenge with each of the three vaccines produced significant levels of antibody but were not protected, whereas treatment with combinations of poly I-poly C and vaccine resulted in significant protection. These results suggest that the combination of induction of local interferon and an immune response contributes to the protection of mice after exposure to street rabies virus infection.

Oligonucleotide mapping of viral RNA, peptide mapping of virus proteins, and virion RNA termini sequencing all show that long term persistent infection by Vesicular Stomatitis Virus (VSV) leads to extensive and continuous genome mutation. The Dl particles present in persistently infected cells apparently help drive this rapid mutation of infectious virus because serial high multiplicity passages of VSV in acute lytic infections generates more oligonucleotide map changes in virus RNA than does alternating high and low m.o.i. passage, or low m.o.i. passage. Furthermore, virus populations in persistently - infected cultures are selected for resistance to the Dl particles present initially in the carrier cultures. The mutant virus clones recovered after many years of persistence contain more than 2% of mutated bases at the 3′ end of virion RNA and about 15% at the 5′ end. The mutant virus recovered after years of persistence does not rapidly revert, and is as stable as the original input virus clone. A number of biologically interesting mutant phenotypes have been recovered from these persistently infected cells. These include: (I) ts smaII plaque, avirulent mutants; (2) mutants resistant to Dl particles originally present in the persistently infected cells; (3) mutants which give extremely low virus yields on initial isolation and which are able to establish persistent infection without added Dl particles; (4) mutants selected in vivo which allow persistently infected cells to form tumors and metastases in nude mice (these strongly induce interferon and natural killer cells, but escape the natural killer cell surveillance due to virus mutation); (5) mutants arising spontaneously in the carrier cells in culture which are poor inducers of interferon and of natural killer cells, and which also allow carrier cells to form tumors and metastases due to viral mutations; (6) mutants which show reduced neutralization kinetics with heterologous and homologous antisera; (7) mutants exhibiting apparent smaller size M protein, or a major new virion protein band near the G protein; (8) mutants which have lost all mouse virulence (VSV and rabies virus), and mutants which acquired mouse virulence (rabies HEP Flury vaccine strain). Many of the phenotypes must involve multiple mutations and a number of them may be due to the same mutation(s). Considerable further work will be required to map and understand these phenotypes, but they should provide considerable insight into virus functions. It is clear from this work that RNA virus genomes have an unexpected degree of mutational plasticity, and that viral persistence is a highly competitive, metastable situation which shows no signs of stabilizing as viral genomes and Dl particle genomes evolve over many years.

The antiviral agents cytosine arabinoside, adenine arabinoside, and 6-azauridine were shown to inhibit the replication of rabies virus in vitro but not the replication of Sindbis virus. These same drugs were not effective in reducing the mortality rate in mice challenged with street rabies virus.

The protective effect of the interferon inducer, polyriboinosinic-polyribocytidylic acid (poly I:C), was studied in rabbits and mice experimentally infected with street and fixed strains of rabies virus. Six daily intravenous inoculations of 1.0 mg or 0.5 mg of poly I:C, beginning 3-24 hr before viral challenge, protected all rabbits infected with fixed virus. Three daily intramuscular injections of 0.5 mg of poly I:C, beginning 3 hr after viral challenge, protected rabbits infected with street virus. Experiments with fewer injections of poly I:C were not done. Intramuscular injections of poly I:C produced a local interferon response, and a suggestion of better protection was seen in rabbits given poly I:C in the same muscle site as the virus. Street virus-infected mice were protected by as little as 1.3 pig of poly I:C, and the intramuscular route of injection gave better protection than the intraperitoneal route. Protection could be seen in mice inoculated with poly I:C as long as 67 hr after injection of street virus.

Fifty-two instances of opportunistic lung disease were reviewed with regard to their roentgenologic presentation and course. Familiarity with the underlying disease and its therapy must be brought into focus with an understanding of the differing patterns of opportunistic lung disease both clinically and roentgenologically.Emphasis should be placed on the alveolar nature of Pneumocystis carinii pneumonia rather than the previously described interstitial, perihilar roentgenographic pattern. In its florid presentation, diffuse alveolar opacification of the lung fields is the hallmark of this disease roentgenologically.Nocardiosis should be suggested by an infiltrative or nodular lesion with cavitation, particularly in a patient having undergone transplantation and subsequent immune suppression.The aggressive tendencies of the Phycomycetes in a small group of patients were characterized by fistula formation, vascular and tracheobronchial invasion.By comparison, the benign ill-defined nodular infiltrates of c...

The patient described herein died with bacteremia and septicopyemia caused by Providencia stuartii. The apparent rarity of this occurrence may not be real, since laboratory recourse to the epithet, "paracolon," probably hides infections actually caused by Providencia species. Assay of virulence by determination of acute median lethal doses (LD 50 ) for mice (intraperitoneal injection), using strains of Providencia species (two from the blood of our patient; six from the urine of other patients), revealed a population of relatively low virulence (LD 50 in the range of 10 4 to 10 6 bacilli) and high virulence (LD 50 in the range of 1 to 50 bacilli). Of the twelve antimicrobial agents tested simultaneously and identically in vitro , kanamycin and gentamicin were the most effective. Carbenicillin and rifamycin-AMP were equally potent and appear to warrant trial in therapy because of lesser liability of toxicity in man.