Evaluation of interferon and interferon inducers as antiviral agents: Animal studies

Kern, Earl R.; Glasgow, Lowell A.

doi:10.1016/0163-7258(81)90065-6

Cited by 12 publications

(5 citation statements)

References 123 publications

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“…Protective activity against both systemic and local infections of the eye, skin, and genital tract have been demonstrated (4)(5)(6)(7)(8)(9)(10)(11). In this study we describe the antiherpetic activity of an IFN-a analog, IFN-aConl, against both lethal systemic and acute cervicovaginal HSV type 2 (HSV-2) infections in hamsters.…”

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confidence: 99%

Antiherpetic effects of a human alpha interferon analog, IFN-alpha Con1, in hamsters

Fish¹,

Banerjee²,

Levine³

et al. 1986

Antimicrob Agents Chemother

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The efficacy of a novel consensus form of human alpha interferon designated IFN-aCon1 was evaluated against herpesvirus infections in vitro and in vivo. At comparable antiviral concentrations, natural lymphoblastoid IFN, IFN-aConj, the molecular subtype , and the hybrid IFN-aAD(Bgl) obtained by recombinant DNA methods conferred similar protection against herpes simplex virus type 1 and type 2 (HSV-2) infections of human cells in vitro. Whereas 7 X 10 U of IFN-aAD(Bgl) administered in 7 intraperitoneal (i.p.) doses between -4 and 96 h relative to infection protected 90% of mice from a lethal HSV-2 infection, a similar treatment regimen with IFN-aCon, conferred no protection. Systemic HSV-2 infection of hamsters was rapidly lethal, but a single i.p. treatment with 106 U of either IFN-aCon, or IFN-aAD(Bgl) was highly effective and protected 90 and 75% of animals, respectively, when given 6 h before infection; treatment with IFN-aCon, protected 45% of animals when administered 10 h after infection. In addition, IFN-aCon, was highly protective against acute cervicovaginal HSV-2 infection of hamsters when administered either in a single i.p. dose of 106 U at -6 or 10 h relative to infection or in multiple i.p. doses of 106 U between -6 and 120 h relative to infection. Protection was manifested by a delay in the onset of and a reduction in duration of infection, a reduction in the number of positive cervicovaginal infections, and an increase in the survival rate.The interferons (IFNs), by virtue of their potent antiviral (16) and immune regulatory (13) activities, have provided evidence of efficacy against herpes simplex virus (HSV) infections. Protective activity against both systemic and local infections of the eye, skin, and genital tract have been demonstrated (4)(5)(6)(7)(8)(9)(10)(11). In this study we describe the antiherpetic activity of an IFN-a analog, IFN-aConl, against both lethal systemic and acute cervicovaginal HSV type 2 (HSV-2) infections in hamsters. MATERIALS AND METHODSIFNs. An analog of the natural IFN-a subtypes (17) (-4, 2, 24, 36, 48, 72, 96 h)

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confidence: 99%

Antiherpetic effects of a human alpha interferon analog, IFN-alpha Con1, in hamsters

Fish¹,

Banerjee²,

Levine³

et al. 1986

Antimicrob Agents Chemother

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“…Protective activity against this virus has been reported for both systemic and local infections of the eye, skin, and genital tract (10,11; J. C. Overall, Jr., T. J. Yeh, and E. R. Kern, Program Abstr. Intersci.…”

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confidence: 99%

Enhanced efficacy of the acyclic nucleoside 9-(1,3-dihydroxy-2-propoxymethyl)guanine in combination with beta-interferon against herpes simplex virus type 2 in mice

Fraser-Smith¹,

Eppstein²,

Marsh³

et al. 1984

Antimicrob Agents Chemother

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The acyclic nucleoside 9-(1,3-dihydroxy-2-propoxymethyl)guanine (DHPG) and natural mouse interferon beta (MuIFN-P) were evaluated for their efficacy alone and in combination against herpes simplex virus type 2 systemic infections in mice. Intraperitoneally infected animals were treated once a day with the drugs at various concentrations for 5 days starting 24 h after inoculation. DHPG was injected subcutaneously at doses of 0.7 to 6 mg/kg. MuIFN-,B was given intraperitoneally at doses ranging from 3 x 103 to 3 x 104 IU per mouse. For DHPG alone, the effective dose at which 50% of the mice survived (ED50) was >6 mg/kg.However, when given in combination with an ineffective dose of MuIFN-_B (104 IU per mouse), the ED50 for DHPG was 0.8 mg/kg. In addition, at the highest dose tested, MuIFN-P alone had no protective activity against herpes simplex virus type 2 (ED50, >3 x 104 IU per mouse). However, when given in combination with a marginally effective dose of DHPG (2 mg/kg), the ED50 for MuIFN-, was <3 x 103 IU per mouse.

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“…Recognition of PAMPs, such as dsRNA structures, by TLRs or RIG-I-like receptors activates signal-transduction pathways that culminate in the production of antiviral effector molecules capable of stemming virus spread (1)(2)(3). Type I IFN (IFN-I) is considered the main antiviral cytokine capable of inducing a large number of protective molecules (4)(5)(6). Activation of antiviral immune responses is also associated with a range of inflammatory signals that trigger the activation of caspases, IL-1b production, and inflammatory cell recruitment (7)(8)(9)(10).…”

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confidence: 99%

A Plant-Derived Nucleic Acid Reconciles Type I IFN and a Pyroptotic-like Event in Immunity against Respiratory Viruses

Kasumba

Hajake

et al. 2017

The Journal of Immunology

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Nucleic acids carrying pathogen-associated molecular patterns trigger innate immune responses and are used to activate host immunity. Although synthetic nucleic acids have been used for that purpose, they have shown limitations for in vivo and clinical applications. To address this issue, we tested a naturally occurring dsRNA extracted from rice bran (rb-dsRNA) and characterized it as a potent ligand of TLR3 and MDA5. In this study, intranasal administration of rb-dsRNA induced production of type I IFNs by alveolar macrophages and protected mice from morbidity and mortality resulting from respiratory virus infection, such as influenza A virus. This protection was completely absent in mice lacking both TRIF and MDA5, indicating the essential role of TLR3- and MDA5-dependent pathways. Interestingly, IFNAR1-deficient mice retained residual antiviral protection, which was abolished by pharmacological inhibition of caspase 1, but not IL-1β signaling. In fact, rb-dsRNA activated caspase 1 via TRIF, resulting in the release of IL-1β and LDH. In addition to the direct antiviral activity, rb-dsRNA modulated the immune cell population in the lungs by repopulating virus-depleted alveolar macrophages. Our data demonstrate that rb-dsRNA orchestrates IFN-dependent and -independent direct antiviral protection and that it is a potent immune stimulator modulating antiviral immunity in the lungs. These findings open doors to a range of precise immune-modulating studies and therapeutic options.

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Evaluation of interferon and interferon inducers as antiviral agents: Animal studies

Cited by 12 publications

References 123 publications

Antiherpetic effects of a human alpha interferon analog, IFN-alpha Con1, in hamsters

Antiherpetic effects of a human alpha interferon analog, IFN-alpha Con1, in hamsters

Enhanced efficacy of the acyclic nucleoside 9-(1,3-dihydroxy-2-propoxymethyl)guanine in combination with beta-interferon against herpes simplex virus type 2 in mice

A Plant-Derived Nucleic Acid Reconciles Type I IFN and a Pyroptotic-like Event in Immunity against Respiratory Viruses

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