Antiviral activities of mouse

Since interferons appear to be species-specific, we investigated whether the ganglioside fraction from mouse brain was more potent in inhibiting antiviral activity of mouse fibroblast interferon than that obtained from heterologous brain extracts. As seen in Figure 1 bovine brain gangliosides were almost as potent... 

Figure 1. Effects of mouse ( ) and bovine (Q) brain gangliosides on antiviral activity of mouse fibroblast interferon...

Since the ceramide portions of more and less inhibitory glycoliplds are very similar, differential Inhibition of antiviral activity of mouse fibroblast interferon must be related to their carbohydrate side chains. We therefore assayed antiviral activity in the presence of various saccharides contained in gangiiosides. As seen in Figure 3, both N-acetylneuraminyl lactose and N-acetyl-neuraminic acid inhibited antiviral activity, requiring approximately equal concentrations to obtain complete inhibition (60 mM). However, in comparison to GM3, 600-fold higher concentrations of these sugars had to be employed to yield complete inhibition of antiviral activity. N-glycolyineuraminic acid and the 6-methyi-... 

Figure 7. Effects of bovine brain gan-gliosides on antiviral activities of mouse fibroblast and T-cell interferons...

Hybrid and Consensus IFNs. After the sequences of all IFN-a subtypes and their activities were deduced, recombinant hybrids were designed to improve the activity of natural subtypes. It is possible to radically change the properties of an IFN by making hybrids. For example, a hybrid made from the first 61 amino-acid residues of IFN-al and the last 104 amino-acid residues of IFN-a2 exhibited high antiviral activity on mouse cells, while another hybrid produced from the first 91 amino-acid residues of IFN-al and the last 72 amino-acid residues of IFN-a4 had no antiviral effect but displayed enhanced antitumor activity in mice, a property neither of the parent molecules exhibit. Structure-function analysis of hybrid molecules has indicated that the NH2 terminus portion of the IFN-a molecule is important for its biological activity [46]. 

In this communication we extend our earlier observations, which primarily dealt with the antiviral action of mouse fibroblast interferon, to its antigrowth activity and to antiviral and antigrowth activities of mouse T-cell interferon. We will show that inhibition by common gangiiosides Is restricted to both activities of fibroblast interferon alone. T-cell interferon, although its biological activities are analogous to those of fibroblast Interferon, neither binds to nor Is inhibited by these glycol ipids. Furthermore we demonstrate that mouse leukemia L—1210 cells that were selected for resistance to fibroblast interferon (6), respond equally well to T-cell Interferon as the parent cells which are responsive to both Interferons. 

It was discovered in 1998 that expression of IDO activity in the mouse fetus represses the maternal T-cell activity and hence protects the fetus from the maternal immune system. Pregnant mice treated with the IDO inhibitor 1-methyltryptophan rejected the embryos via their immune system, thus either IDO itself or a product of tryptophan catabolism is able to suppress the maternal T-cell activity. IDO is also expressed in response to interferon 7 from activating T-cells, inhibiting T-cell proliferation and contributing toward the antiviral activity of interferon 7. The end product of the L-tryptophan degradation pathway, quinolinic acid, has neurological effects, hence the IDO pathway is implicated in several mammalian regulatory pathways. 

With regard to the mechanism of its possible antiviral activity, we have observed an increase in interferon production by ascorbic acid following stimulation of mouse L cell cultures with poly (rI) poly (rC) (Siegel, 1975). We have also noted an enhancement of interferon production vivo following stimulation with Rauscher leukemia virus in BALB/c mice treated with 250 mg% L-ascorbic acid in the drinking water (Siegel, 1974). Thus, the antiviral activity of ascorbic acid may be due, in part, to enhanced interferon production however, the mechanism of this effect remains to be elucidated. 

Prodrugs of DME>C were also synthesized and evaluated to be active against P388 mouse leukemia in vivo. Antiviral activity of DMDC and its derivatives were reported to be effective against HSV-1, VZV, and HCMV.4l.43... 

Table 1. Antiviral activity of various azido, amino, 2 ,3 -unsaturated, and 2, 3 -dideoxy analogues of pyrimidine deoxyribonucleosides on the replication of M-MuLV in 3T3 mouse cells. ...

Pretazettine (395) has been the subject of numerous biological studies, and it has been shown to exhibit a number of interesting activities (96,97,101,178-187). For example, 395 was found to inhibit HeLa cell growth as well as protein synthesis in eukaryotic cells by interfering with the peptide bond formation step (97,101). Furthermore, pretazettine inhibited the purified RNA-dependent DNA polymerase (reverse transcriptase) from avian myeloblastosis virus, a typical C-type virus (178), in an unusual fashion since it physically combined with the polymerase enzyme itself rather than interacted with the nucleic acid template. Pretazettine also exhibited antiviral activity against the Rauscher leukemia virus in mouse embryo cell cultures by suppressing viral replication (179). 

Anti-HIV-1 Activity of Calanolides in Hollow Fiber Mouse Evaluation of (-l-)-calanolide A (1) in a hollow fiber culture-based in a SCID mouse assay of antiviral efficacy indicated that (+)-calanolide A exhibited significant anti-HIV-1 activity after oral or parenteral administration on a once-daily (200mg/kg/ dose) or twice-daily (150 mg/kg/dose) treatment. Furthermore, a synergistic effect was observed in the combination of (-l-)-calanolide A and AZT. ... 

Several interesting organoselenium compounds exhibit antiviral activities. One such is selenazofurin 113, effective against different types of viruses (herpes simplex, parainfluenza and rhinovirus). The purine analogue, 7-methyl-8-selenoguanosine 114, has been tested in vivo for antiviral activity against Semliki Forest virus infection in a mouse model... 

Table 4. Antiviral and cytotoxic activities of some distamycin derivatives. The activity of distamycin derivatives was tested on mouse embryo cells infected or not with MSV (M), ID o Inhibiting dose 50% 77 = therapeutic index, 77>so-cell/72)50-virus...

Olszewska W, Ispas G, Schnoeller C et al (2011) Antiviral and lung protective activity of a novel RSV fusion inhibitor in a mouse model. Eur Respir J 38 401 108... 

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