Clinical Effects of the Recombinant Feline Interferon-ω on Experimental Parvovirus Infection in Beagle Dogs Kenji ISHIWATA, Tomonori MINAGAWA and Tsunesuke KAJIMOTO 1) Department of Microbiology, School of Medicine, Hokkaido University, Sapporo 060–8638 and 1) Animal Health Products Development, Chemicals Business Development Department, Toray Industries, Inc., Tokyo 103–8666, Japan (Received 4 December 1997/Accepted 22 April 1998) ABSTRACT. The clinical effects of recombinant feline interferon-ω (rFeIFN-ω), produced in silkworm by recombinant baculovirus, were examined in 3–4 month-old beagle dogs given an experimental canine parvovirus type-2 (CPV-2) infection. Clinical symptoms, such as pyrexia, vomiting, anorexia and diarrhea, were observed on day 4 after oral inoculation of 10 7 TCID 50 of CPV-2 (cc 238 strain) in almost all the inoculated dogs. From day 4, rFeIFN-ω (1 mega units/kg/day) or physiological saline was administered intravenously to infected dogs for 3 consecutive days. Seven out of 17 dogs treated with physiological saline showed hemorrhagic diarrhea and continuously expressed severe clinical enteritis; one dog died with a large amount of hemorrhagic rice-water stool on day 6 after viral exposure. In contrast, 4 out of 12 dogs treated with rFeIFN-ω showed severe clinical enteritis associated with intermittent diarrhea. Scoring of fecal condition revealed that treatment with rFeIFN-ω significantly shifted the enteritis from a severe to mild form. Furthermore, rFeIFN-ω administered in the morning decreased the number of dogs expressing clinical enteritis in the evening suggesting a rapid effect. Vomiting and anorexia were also improved by treatment with rFeIFN-ω. These results suggest that rFeIFN-ω can reduce severe enteritis caused by CPV-2 infection in dogs. — KEY WORDS: beagle dog, canine parvovirus, enteritis, experimental infection, recombinant feline interferon-ω. J. Vet. Med. Sci. 60(8): 911–917 Outbreaks of canine parvovirus type-2 (CPV-2) infection are characterized by high morbidity and mortality, and have spread rapidly worldwide since 1978 [11, 23]. The appearance of new subtype of this virus generally present less severe disease in dogs that have a better survival rate [24, 26]. However, puppies born in breeding populations have greater risk of infections that are often fatal [5]. Adult dogs kept outdoors often manifest clinically severe symptoms, especially those dogs with an accompanying parasitic infection. Although modified live vaccines are now available, treatment for this disease is still symptomatic and based simply on principles of good supportive care [3, 26]. This infection, when accompanied by severe gastroenteritis, is one of the most important diseases of dogs. It is now clear that interferons (IFNs), identified firstly by Nagano and Kojima [21] and later named by Isaacs and Lindenmann [9], can modulate a number of cellular and immune functions, as well as affect virus replication [28]. The potent antiviral and antitumor activity of IFNs has been used therapeutically in humans [8], and tried in cattle [12], horses [16], and pigs [13]. Recombinant feline interferon-ω (rFeIFN-ω ), produced in silkworm larvae using a baculovirus vector [27, 33], has shown antiviral activity against infection with feline calicivirus, herpesvirus and enteropathogenic virus [19, 35]. Further, Tateyama et al. [30] demonstrated growth inhibitory activity of rFeIFN-ω on canine tumor-cell lines, even though IFNs express a relatively high degree of species specificity. In the present study, we examined the clinical effects of rFeIFN-ω on CPV-2 infection in beagle dogs. MATERIALS AND METHODS Experimental animals: Specific pathogen free beagle dogs (NRD strain) 3 to 4 months of age were obtained from Hokudoh Co., Ltd., Hokkaido, Japan and housed in individual cages during the course of the experiments. These dogs had no antibody to CPV-2 (titer ≤ 1:4) just before viral inoculation. At the end of experiments, all dogs were sacrificed under anesthesia according to the guideline for Animal Experiments, Hokkaido University, School of Medicine. Virus: Canine parvovirus (CPV; cc 238 strain) was used. The strain was originally isolated in Okayama Prefecture, Japan in 1991, from the feces of a dog with vomiting, diarrhea and hemorrhagic stool. The strain was established in Crandell feline kidney (CRFK; ATCC CCL 94) cell cultures at the Tsukuba Central Laboratories, Kyoritsu Shoji Company, Ibaraki, Japan. The virus is identified as a type CPV-2a by its reactivity to specific monoclonal antibodies. Virus suspensions containing 10 7 TCID 50 were inoculated orally. The dogs were diagnosed with CPV-2 infection based on the presence of clinical signs, and the infection was confirmed by seroconversion and detection of viral DNA in rectal feces by a PCR method. Clinical observations and score of clinical symptoms: Rectal temperatures, vomiting, appetite and fecal condition were recorded daily for 2 weeks, and twice daily in the morning and in the evening from day 3 to 10 after virus inoculation. Rectal temperature of over 39.5 C was expressed as pyrexia. The degree of vomiting, appetite and fecal condition were expressed by scores shown in Table 1. For scoring the clinical symptoms, the degree of symptom