Friend virus-induced inhibition of eosinophil granulocyte exudation in mice.

Exudation of eosinophil polymorphonuclear leukocytes (E-PMN) in response to tetanus toxoid (TT) was studied in DBA/2HaD mice with erythroleukemia induced by Friend virus (FV). The inhibition of exudation that developed was independent of increased levels of serum corticosteroids and occurred in surgically adrenalectomized mice. Thus it was independent of steroid-induced effects on E-PMN. The accumulation of neutrophil polymorphonuclear leukocytes (N-PMN) in TT-induced exudates was unaltered. Furthermore, N-PMN exudation in response to other inflammatory stimuli was similarly unimpaired in virus-infected mice, which confirmed the specificity of the inhibition for E-PMN. The virus entity in the FV complex responsible for the effect was not identified. Friend murine leukemia virus, the indigenous helper virus for the defective spleen focus-forming virus, alone, was incapable of inducing the inhibition. It is possible that the lack of participation of E-PMN in TT-induced immune inflammatory exudates in FV-infected mice reflects an unresponsiveness that contributes to the development and progression of leukemia in FV-infected mice.

Effect of split low dose total body irradiation on SFFV mRNA, genomic DNA and protein expression in mice infected with the Friend virus complex.

DBA/2 mice infected with lethal dosages of Friend virus complex (FVC) can be 100% cured by split-dose total body irradiation (TBI) at 150 cGy, an effect associated with the restoration of the cellular immunity which is compromised by the virus. The exact mechanism underlying the curative effect is unknown, but it may involve the interferon (IFN) system and interleukin-2 (IL-2) production. Initial studies indicated that TBI did not directly inactivate the virus, suggesting that irradiation either acted on the target cells for virus replication or on other cells mediating the effect. We have now examined the effect of this relatively low dose TBI on replication, transcription, and protein expression of the Friend virus. Northern blot analysis revealed that in FVC infected mice treated with curative low dose TBI, no spleen focus-forming virus (SFFV)-specific mRNA species were detected. Southern blot analysis revealed that a 6.0 kb SFFV fragment could be detected in infected, untreated spleen cells, but not in cells from FVC-infected mice treated with TBI, or in uninfected spleen cells. Western blot analysis revealed that the SFFV envelope glycoprotein was expressed in the spleen cells from untreated FVC infected mice, but not in the cells from TBI treated FVC infected mice. These results, consistent with our previous findings of greatly reduced spleen focus forming units in mice with FVC which had been treated with this regimen of TBI, suggest the possibility of using such treatments in other retroviral associated disorders.

Antiretroviral activities of hypericin and rose bengal: photodynamic effects on Friend leukemia virus infection of mice.

The ability of hypericin to protect mice from splenomegaly resulting from infection with Friend leukemia virus (FLV) was re-examined in light of recent evidence showing that light is absolutely required for this drug's antiviral activity. FLV-induced splenomegaly was not prevented or ameliorated in mice injected with 100 micrograms hypericin, either mixed with the FLV inoculum or administered 1 day p.i., either under normal laboratory light or in the dark. These results contradict previous findings. Both hypericin and rose bengal, however, inactivated the FLV inoculum at low doses (< 11 micrograms), provided that the mixture was illuminated for 1 h under a normal fluorescent desk lamp. This procedure protected mice completely from FLV-induced splenomegaly, and provided a possible explanation for the discrepancy between our results and those reported previously. We conclude that for FLV, as for other enveloped viruses studied previously, illumination of hypericin with the virus is absolutely required for hypericin's antiviral (virucidal) effects, thus limiting its potential usefulness as an antiretroviral agent.

Differential susceptibility of spleen focus-forming virus and murine leukemia viruses to ansamycin antibiotics.

The streptovaricin complex (SvCx) and rifamycin SV derivatives display potent antiviral activity against the polycythemic strain of Friend leukemia virus (FV-P), as measured by a reduction in the number of spleen foci produced in mice. Such reductions may be explained by inactivation of functions of (i) the spleen focus-forming virus (SFFV), (ii) its "helper" murine leukemia virus (MuLV), or (iii) both viruses normally present in FV-P. We noted that preincubation of FV-P with fractionation products of SvCx, or derivatives of rifamycin SV, at low concentrations (3 to 5 mug/ml) reduces the number of spleen foci 80 to 97%, whereas titers of MuLV (from the same inoculum) remain unaffected (MuLV titers were measured by XC, S(+)L(-), and "helper activity" assays). Our findings indicate a remarkable biological selectivity of ansamycins, as well as nonansamycin components of SvCx, against the transforming and defective spleen focus-forming virus as compared to MuLV. Thus, the drugs might be useful in distinguishing other types of oncornaviruses.

XC cell fusion by murine leukemia viruses: fusion from without.

Concentrated murine leukemia virus (MuLV) or MuLV producing cells induce XC cell fusion within an hour leading to syncytia formation. While MuLV inactivated by UV irradiation, beta-propiolactone or hydroxylamine treatment still caused cell fusion, Bromelin- or trypsin treated MuLV was no longer able to fuse XC cells. Though sonicated MuLV induced no XC cell fusion, it interfered with cell fusion as caused by untreated MuLV. XC cells infected by diluted MuLV of a titer lower than 1 X 10(5) PFU/ml formed no syncytia although they produced MuLV. The cell fusion mechanism is discussed.