Remission of leukemia and loss of feline leukemia virus in cats injected with Staphylococcus protein A: association with increased circulating interferon and complement-dependent cytotoxic antibody.

Abstract

We have injected purified Staphylococcus aureus protein A intraperitoneally into leukemic cats infected with feline leukemia virus, into cats persistently infected with feline leukemia virus but without hematologic or cytologic abnormalities, and into healthy cats without feline leukemia virus infection. Pre-and post-treatment serum samples were evaluated sequentially for interferon activity and for complement-dependent cytotoxic antibody. Our results indicate that serum interferon increased dramatically (<3 to 324 units/ml) during treatment only in cats that responded to staphylococcal protein A therapy. Increase of interferon preceded or was closely associated with increasing levels of cytotoxic antibody, loss of viremia, and correction of cytological and hematological abnormalities of three leukemic cats. The cytotoxic antibody was shown to be specific for envelope glycoprotein gp7O of the feline leukemia virus. One persistently feline leukemia virus-infected cat without leukemia that became nonviremic also developed high levels of interferon and specific cytotoxic antibody. By contrast, interferon levels of cats not responding to treatment had levels of <3 to 27 units/ml. Normal healthy cats injected with staphylococcal protein A showed moderate transient increases of interferon but no detectable cytotoxic antibodies to FL-74 cells. These data suggest that interferon and cytotoxic antibody may play important, possibly complementary roles in inducing remission of leukemia and loss of viremia in cats treated with staphylococcal protein A.Remission of leukemia-lymphoma associated with disappearance of feline leukemia virus (FeLV) (4,5), IFN activity and complementdependent cytotoxic antibody were studied in sera of several cats that had been injected i.p. with SPA. It will be shown that regression of malignancy and loss of evidence of virus infection occurred in cats that experienced first an increase in IFN that was followed by appearance and usually progressive increase of a complement-dependent cytotoxic antibody directed against a virus-infected feline lymphoma cell line. MATERIAL AND METHODSAnimals. Pet cats were selected for treatment by ex vivo immunoadsorption (2, 3) or by injection with purified SPA (Pharmacia, Uppsala, Sweden). The SPA injections were given i.p. (20 pug/2.75 kg of body weight) twice weekly for 10-12 weeks. Bone marrow and peripheral blood smears were evaluated prior to treatments and after every 10th treatment. FeLV status was determined biweekly by indirect immunofluorescence assay (IFA) (6) and enzyme-linked immunosorbent assay (ELISA) as described (2). Pre-and posttreatment serum samples were stored at -70'C until assayed for IFN and cytotoxic antibody.Feline IFN Assay. Feline IFN was assayed by a modification of the microplaque reduction method (7), using approximately 40 plaque-forming units (pfu) of vesicular stomatitis virus (VSV) per well on FFC-9 cells (fetal cat fibroblast cell line kindly provided by N. C. Pedersen, University of California, Davis). An IFN concen...

Feline leukemia virus: current status of the feline induced immune depression and immunoprevention

“…They see regression of lymphosarcoma in the absence of a detectable antiviral immune reaction as base or no increase in 1FN levels. These data contrast with those of Liu et al [102] who show that intraperitoneal infusion of SPA induces increases in circulating interferon levels and complement-dependent cytotoxic antibody. Recent data accumulated in this laboratory support some of the findings of Harper et al [104].…”

“…The increase in CL responses in ncutrophils from FeLV-viremic cats may be accounted for, in part, by an increase in virus-free neutrophils in the peripheral blood. Liu et al [102] also report improvement in bone marrow cytology during treatment with SPA and posttreatment. Improved in vitro lymphocyte activation has been reported when human lymphocytcs are incubated with autologous serum treated with SPA [101].…”

“…Liu et al [101,102] report dramatic improvement in FcLVinfected cats treated with SPA by ex vivo and in vivo immunoadsorption. Their studies indicate induction of cytotoxic antibody to viral gp70 by the ex vivo regimen.…”

Alpha interferon (2b) in combination with zidovudine for the treatment of presymptomatic feline leukemia virus-induced immunodeficiency syndrome

“…Studies by Liu et al (26,27) suggest that a reduction in circulating FeLV antigenemia may be associated with a reversal of hypocomplementemia and a return of endogenous IFN and virus-specific neutralizing antibody production to normal levels, leading to the eventual reversal of viremia. In HIV-induced immunodeficiency disease in humans, a positive response to IFN-a treatment has been correlated with the level of pretreatment antigenemia (13), while progression to clinical AIDS is 20-fold greater in males who are seropositive and antigenemic (12).…”

Prospects for Antiviral Chemotherapy in Veterinary Medicine: 1. Feline Virus Diseases

“…Calici virus (FCV) ribavirin Povey(1976Povey( ,1978b Day et al (1984) ex vivo Jones et al (1980) immunosorption + l.p, Liu et al (1984aLiu et al ( , 1984b AZT, PMEA, IFN Hoover et.al. (1990a); ddC Hoover et al (1990b); Zeidner et al (1990a); Tavares et al (1989) Polas et al (1990); Zeidner et al (1989) AZT± IFN ++ Zeidner et al (1990aZeidner et al ( , 1990bZeidner et al ( , 1990c) AZT ++ Mathes et al (1990) ++ Tavares et al (1987) dextran sulphate Mathes et al (1991) Koolen et al (1990) Weiss et al (1990) virus-infected cells.…”