Induction of Interferon and Viral Resistance i n Animals by Polynucleotides

S, Baron; Buy, H. Du; Buckler, Charles E.; Johnson, Martin L.; Park, J.; Billiau, Alfons; Sarma, Padman S.; Huebner, R. J.

doi:10.1111/j.1749-6632.1970.tb53446.x

Cited by 13 publications

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“…At one time it was thought that viral stimuli gave rise to neutral or slightly acidic interferons of molecular weights of about 30,000, and that nonviral stimuli produced much larger, more basic, and usually less stable interferons. This view has proved to be an oversimplification, since the kind of interferon that is formed may depend on the following other factors: (a) the nature of the inducing stimulus (75), (b) whether induced in vivo or in cultured cells (76), (c) the type of cultured cell (77,78,94), (d) the nature of the stimulated organ in the intact animal (79), (e) the time interval between stimulation and harvest (80),1 (f) the presence of stimulus enhancers (81), (g) the degree of stimulation (82), and (h) unexplained changes with time of the interferon producing animal strain (83).…”

Section: Multiplicity Of Interferonsmentioning

confidence: 99%

Interferons: Purification and Physicochemical Aspects

Fantes¹

1970

The Journal of General Physiology

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Antiviral interferon activity in any one species can be exhibited by a variety of substances that differ in their physical and chemical properties, but the nature of these differences is not understood. Conditions that can lead to the formation of diverse types of interferons have been outlined. Reasons have been adduced why, for certain purposes, purification of interferons is desirable or even necessary, and examples have been presented to show how and to what extent this has been achieved. In spite of some very high purification factors, not a single interferon has been obtained as a pure substance. Therefore, all available knowledge of physical and chemical properties has been obtained by indirect means.The first interferon was discovered by Isaacs and Lindenmann (1) in 1957, and since then many biochemists have attempted to purify many interferons. It is perhaps worthwhile to pause for a moment and consider why it is sometimes necessary, or at least desirable, to work with purified rather than with crude interferons. WHY PURIFY INTERFERONS?Experiments with crude interferons have on several occasions led to wrong interpretations, and examples that show how this danger was sometimes overcome by purification or other means are presented. There are at least five situations where the use of crude interferons is inappropriate.Firstly, crude interferons, but also sera and tissue extracts from apparently normal animals, culture fluids from uninfected cells, urine, allantoic fluid, egg white, agar overlays, etc., frequently contain other often nonvirus-and nonspecies-specific antiviral substances that may simulate certain aspects of interferon action and may thus mislead the casual observer. A number of specific and nonspecific viral antagonists of this nature is shown in Table I which represents the "list of contents" of a recent'review article by Wassermann (2). But there are doubtless others, e.g. Buckler and Baron (3) showed that heterologous, acid-stable, antivaccinia virus activity of crude mouse sThe Journal of General Physiology interferon and of mouse serum could be readily removed from chick cells by mere washing. The same process also eliminated, again from chick cells, a noninterferon antivaccinia factor, present in normal allantoic fluid. Andrews (4) found that crude chick, calf, monkey, and human interferons had pronounced activity against vaccinia virus in rabbit skin, and even the noninfected, heterologous culture fluids themselves were active in this system. Similarly, the size of vaccinia lesions and the degree of necrosis in monkey skin were not reduced only by monkey interferon, but also by crude chick interferon. We, (5, 6) in collaboration with Doctors Andrews and Finter, found that crude allantoic chick interferon also had some activity in human embryonic lung cells and in mouse L cells against rhino-and Sendai viruses, respectively, but that partly purified and concentrated interferon, with much higher potency in chick cells, had lost its heterologous activity. Sutton and Tyrrell (7)...

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Section: Multiplicity Of Interferonsmentioning

confidence: 99%

Interferons: Purification and Physicochemical Aspects

Fantes¹

1970

The Journal of General Physiology

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“…5 a) or 0.016 mg/kg (Fig. 5 c) exogenous interferon and interferon inducers were administered in arbitrarily chosen dosages and the treatment regimen used for (poly rI)-(poly rC) (and Newcastle disease virus) was likely to lead to hyporeactivity (10,28,36,37). Moreover, circulating interferon titers were not determined, so that the efficacy of exogenous versus endogenous interferon treatment could not be compared on the basis of interferon titers obtained in the animal.…”

Section: Resultsmentioning

confidence: 99%

The role of interferon in the protective effect of a synthetic double-stranded polyribonucleotide against intranasal vesicular stomatitis virus challenge in mice

Clerco¹,

Nuwer²,

Merigan³

1970

J. Clin. Invest.

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A B S T R A C T Intravenous injection of polyinosinic acid/polycytidylic acid [(poly rI) * (poly rC)] offered significant protection against intranasal challenge of young mice with vesicular stomatitis virus (VSV). Optimal protection was obtained when a single dose was administered 2 hr before virus challenge, but repeated doses were effective when started as late as 3 days after virus challenge. The therapeutic ratio or ratio of maximum tolerated dose to minimum effective dose for a single intravenous injection of (poly rI) *(poly rC) 2 hr before virus inoculation was > 8 mg/kg: 0.004 mg/ kg or > 200. Dose-response curves for interferon production and antiviral protection by (poly rI) -(poly rC) were closely parallel. Equivalent doses of poly rI or poly rC alone did not exert any interferon-inducing capacity or protective effect on intranasal VSV challenge. Several factors, which are known to potentiate or antagonize interferon production, increased or decreased the interferon-inducing capacity and antiviral protection of either (poly rI) * (poly rC) or maleic acid/divinyl ether copolymer (MA/DVE) in parallel. Interferon production and antiviral protection by MA/DVE were enhanced by arginine but abolished by prior treatment with MA/DVE; DEAE-dextran (intraperitoneally), kinetin riboside and isopentenyladenosine, and prior injection of endotoxin reduced both interferon production and antiviral protection by (poly rI) -(poly rC).Treatment with exogenous interferon in amounts which closely mimicked the levels of circulating interferon produced endogenously by an effective dose of (poly rI) * (poly rC) gave protection against intranasal

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“…Synthetic polyinosinic polycytidylic RNA (poly I*poly C) has been found to inhibit cytolytic (1-8) as well as oncogenic (8)(9)(10) viruses. In addition, poly I*poly C suppresses the development of transplanted murine (11)(12)(13) and guinea pig (14) tumors of known or unknown viral etiology.…”

mentioning

confidence: 99%

“…In addition, poly I*poly C suppresses the development of transplanted murine (11)(12)(13) and guinea pig (14) tumors of known or unknown viral etiology. Poly 1-poly C is a potent inducer of interferon (1)(2)(3)(4)(5)(6)(7)(8)(9)(10). Synthetic polyribonucleotides enhance humoral and cellular immunological response of mice (15)(16)(17).…”

mentioning

confidence: 99%