Effect of human leukocyte interferon on vaccinia-and herpes virus-infected cell cultures and monkey corneas

Abstract

Pretreatment of human fibroblast cultures with human leukocyte interferon (HIF, 1,000 IU/ml) resulted in a 24-h delay of virus replication after infection with vaccinia virus and herpes simplex virus type 1 and type 2. Additional HIF treatment 24 h after infection effectively lowered the maximum yield of viral infectivity. Equal results were obtained in simian cells with 3,000 IU of HIF per ml. The spread of two cell-bound herpesviruses, varicella zoster virus and Medical Lake macaque herpesvirus, was inhibited by 2,000 IU of HIF per ml in human fibroblasts and Vero cells, respectively. Varicella zoster virus infectivity was notably reduced by HIF, whereas the latter system showed a low sensitivity. To study the effect of HIF in the infected cornea, keratitis was induced experimentally in both eyes of 12 rhesus monkeys and 12 African green monkeys by inoculation with vaccinia virus and herpes simplex virus, respectively. In each monkey one eye served as a control for the full cycle of disease. In the other eye HIF treatment was initiated prophylactically 15 h before or simultaneously with the challenge virus infection or 6 to 20 h postinfectionally or therapeutically after onset of the disease, and the treatment was continued for 2 to 7 days. Prophylactic and simultaneous administration equally resulted in inhibition of both vaccinia and herpes keratitis. Postinfectional and therapeutic administration of interferon moderated the course of keratitis slightly and shortened the period of virus shedding.

Therapy and Long-Term Prophylaxis of Vaccinia Virus Respiratory Infections in Mice with an Adenovirus-Vectored Interferon Alpha (mDEF201)

“…Single daily doses of rIFNa or rIFNc rescued mice from lethality when administered 1-2 days after virus challenge and reduced lung virus titers. Both vaccinia keratitis and vaccinia-induced skin lesions were treated with rIFN (topically and injected respectively) in monkey models with success [10,11]. Vaccinia and other poxviruses have evolved comprehensive mechanisms to antagonize the interferon system [12], that include blocking IFN gene induction, disrupting extracellular and intracellular signaling and slowing IFN induced gene (PKR and 2959 OAS) activation.…”

Comparative evaluation of human leukocyte and fibroblast interferon in the prevention of herpes simplex virus keratitis in a monkey model

“…Another slight difference, which cannot be precisely scored, consisted of a reversible toxic effect on the comneal epithelium, which had been observed previously (6) with HLI in mon- 0 II 2 23 9 VI 6 25 24 III 13 21 62 VII 14 27 52 IV 26 27 96 VIII 29 29 100 a The results ofbiomicroscopic examination were coded by scores of 0 to 4 (0 = no evidence of keratitis; 1 = one or two stellate efflorescence; 2 = single dendritic or multiple stellate efflorescences; 3 = multiple dendritic efflorescences covering more than 50% of the cornea; 4 = geographic ulcers plus dendritic efflorescences covering more than 50% of the cornea). The scores on each of the 2 days of examination (days 3 and 5 postinfection) of all monkeys of each group were added.…”

“…The antiviral effect of topically applied interferon has been demonstrated in herpes simplex virus type 1 (HSV-1)-induced epithelial keratitis in non-human primates and man (5,6,(8)(9)(10). All controlled studies thus far have utilized human leukocyte interferon (HLI).…”

“…HSV-1 keratitis was induced in African green monkeys in the same way as described previously (6), except for the dose of infecting virus, which was 2 x 107 mean tissue culture infective doses per inoculum (0.1 ml), guaranteeing a 100% incidence of keratitis. Ophthalmological examinations, virus isolations, assays of interferon activity, and interferon treatment were performed as described previously (6). HLI was induced in primary human leukocytes by live Sendai virus (1).…”

Selective antiviral activity of human interferons on primate oncogenic and neurotropic herpesviruses

“…was reported for murine cytomegalovirus by Oie et al (1975); for varicellazoster by Postic and Dowling (1977) and Holmes et al (1978) and for vaccinia and herpes simplex virus type 1 and 2 treated with 1,000 IU of human leukocytic IF by Dunnick and Galasso (1979). Neumann-Haefelin et al (1975) reported inhibition by human leukocytic IF on HSV 1 and 2, vaccinia, varicella zoster and medical lake macaque herpesvirus. These reports are in conflict with earlier reports on the influence of the m.0.i.…”