Effect Of The Combination Of Interferon-A And Stavudine On Friend Virus

Sidwell, Robert W.; Warren, Reed P.; Okleberry, Kevin M.; Burger, Roger A.; Morrey, John D.

doi:10.1093/infdis/171.supplement_2.s93

Cited by 4 publications

(4 citation statements)

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“…5). Previous studies reported long-term therapies (12 to 25 days) for FV infection or murine AIDS in which IFN-␣ had an effect on virus replication (13,34,35). We were able to show that a short-term postexposure therapy with IFN-␣ during acute infection induced an antiviral status sufficient to control virus replication and disease progression.…”

Section: Discussionmentioning

confidence: 50%

Effects of Type I Interferons on Friend Retrovirus Infection

Gerlach

Schimmer

Weiß

et al. 2006

J Virol

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Section: Discussionmentioning

confidence: 50%

Effects of Type I Interferons on Friend Retrovirus Infection

Gerlach

Schimmer

Weiß

et al. 2006

J Virol

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“…This result suggests that the PLC ␤2 deficiency does not compromise the host's ability to deal with the bacterial challenge. The mice were also challenged with Friend leukemia virus (FLV), which induces splenomegaly (24). FLV was injected peritoneally, and 2 weeks later the spleens were weighed.…”

Section: Resultsmentioning

confidence: 99%

Roles of phospholipase C β2 in chemoattractant-elicited responses

Jiang

Kuang

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

138

112

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The physiological roles of phospholipase C (PLC) ␤2 in hematopoiesis, leukocyte function, and host defense against infection were investigated using a mouse line that lacks PLC ␤2. PLC ␤2 deficiency did not affect hematopoiesis, but it blocked chemoattractant-induced Ca 2؉ release, superoxide production, and MAC-1 up-regulation in neutrophils. In view of these effects, it was surprising that the absence of PLC ␤2 enhanced chemotaxis of different leukocyte populations and sensitized the in vivo response of the PLC ␤2-deficient mice to bacteria, viruses, and immune complexes. These data raise questions about the roles that PLC ␤2 may play in signal transduction induced by chemoattractants in leukocytes.Phospholipase C (PLC) hydrolyzes phosphatidylinositol 4,5-bisphosphate to produce two important second messengers, inositol trisphosphates and diacylglycerol (1). There are four different PLC ␤ isoforms that have been cloned. They are all regulated by heterotrimeric G proteins, and there is evidence suggesting that different isoforms may be involved in a variety of signaling circuits. The ␤2 isoform is found primarily in hematopoietic cells (2, 3), and it can be activated by both the G␣ subunits of the Gq class and by the ␤␥ subunits generated by a number of different heterotrimeric G proteins (3-9). Cotransfection experiments in COS-7 and HEK cells suggest that PLC ␤2 may function downstream of chemoattractant receptors. Transfection of receptors for complement component C5a and fMet-Leu-Phe (fMLP) (10), interleukin (IL)-8 receptors a and b (11), and CKR-1 and -2 (12) demonstrated that each of the receptors activates PLC ␤2 through the pertussis toxin (PTx)-sensitive release of ␤␥ from the G i class of heterotrimeric G proteins. In addition, this may be a primary signaling pathway in neutrophils, because much of the PLC activity elicited through chemoattractant receptors also appears to function through the G i -mediated release of ␤␥ (13-17).To confirm the existence of the G␤␥-PLC ␤2 pathway in vivo and to investigate the function of the pathway in hematopoiesis and leukocyte function, we generated a mouse line that lacks PLC ␤2. We found that PLC ␤2 is the major isoform that mediates PTx-sensitive PLC activation induced by chemoattractants and that PLC ␤2 is critical to many chemoattractant-elicited responses, including Ca 2ϩ efflux, superoxide production, and up-regulation of MAC-1. However, PLC ␤2 deficiency does not attenuate chemoattractant-induced chemotaxis; surprisingly, it was found to enhance the process. MATERIALS AND METHODS Generation of PLC ␤2-NullMice. An 8-kb genomic DNA from a 129SV agouti mouse strain library contains two exons of the PLC ␤2 gene, and it was used to make the gene-targeting construct. The exons encoded residues 378-464, which are located in the C terminus of the X box. Parts of the exons were replaced with a neomycin-resistance gene. The gene-targeting construct was transfected into embryonic stem (ES) cells (CJ7 clone) by electroporation. After selection with Geneticin, e...

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“…In these animal studies none of the interactions were antagonistic. We have used these synergy determination methods in other published works [21,22].…”

Section: Synergy Determinationsmentioning

confidence: 99%

Combination Treatment of Influenza A Virus Infections in Cell Culture and in Mice with the Cyclopentane Neuraminidase Inhibitor RWJ-270201 and Ribavirin

Smee

Bailey²,

Morrison³

et al. 2002

Chemotherapy

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Treatment of virus infections with compounds acting by different mechanisms may lead to more potent effects when these agents are used in combination. Under this premise, two known active influenza virus inhibitors, ribavirin and the novel cyclopentane influenza virus neuraminidase inhibitor (1S,2S,3R,4R)-3-[(1S)-(acetylamino)-2-ethylbutyl]-4-[(aminoiminomethyl)amino]-2-hydroxy-cyclopentanecarboxylic acid (RWJ-270201, BCX-1812) were studied. Experiments in cell culture demonstrated that RWJ-270201 plus ribavirin synergistically reduced extracellular influenza A/NWS/33 (H1N1) virus yields at low concentrations of each inhibitor. Mice were treated with ribavirin at 20 and 6.25 mg/kg/day combined with RWJ-270201 at 1, 0.32, or 0.1 mg/kg/day, or used alone. Treatments were twice daily for 5 days starting 4 h before exposure to influenza A/NWS virus. Only RWJ-270201 alone at 1 mg/kg/day significantly prevented mortality. In contrast, most drug combinations increased survival significantly compared to the placebo group. Doses of the two compounds used in combination delayed the mean day of death, and improved arterial oxygen saturation levels, as measured on day 11 of the infection. The combination of the two inhibitors produced additive to synergistic interactions in these mouse experiments with no enhancement of host toxicity. Treatment of influenza infections in the clinical setting may benefit by these two agents in combination.

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Effect Of The Combination Of Interferon-A And Stavudine On Friend Virus

Cited by 4 publications

References 0 publications

Effects of Type I Interferons on Friend Retrovirus Infection

Effects of Type I Interferons on Friend Retrovirus Infection

Roles of phospholipase C β2 in chemoattractant-elicited responses

Combination Treatment of Influenza A Virus Infections in Cell Culture and in Mice with the Cyclopentane Neuraminidase Inhibitor RWJ-270201 and Ribavirin

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