Takuo Ishida

Long-term clinical observations on feline immunodeficiency virus infected asymptomatic carriers.

Eleven feline immunodeficiency virus (FIV) infected asymptomatic carrier (AC) cats were observed for 2 years for development of acquired immunodeficiency syndrome (AIDS). Four of the 11 (36.4%) showed progression of the clinical stage. Persistent generalized lymphadenopathy was noted in three cats as the first sign of illness after the AC phase, while the other showed lymphadenopathy with signs of AIDS-related complex. In all four cats the AIDS-related complex stage lasted for 10 months or longer, and two showed progression of the disease into AIDS. The two cats showing AIDS illnesses died within approximately 1 year after they had developed persistent generalized lymphadenopathy. Pathology confirmed the diagnosis of AIDS characterized by the presence of depletion lesions in the lymphoid organs, and of severe infections of an opportunistic nature. The overall mortality of FIV infected AC cats during a 2 year period was two out of 11 (18.2%). These cats showed decreased concanavalin A mitogen response of peripheral blood mononuclear cells as the disease progressed.

The Role of Macrophages in the Early Resistance to Mouse Hepatitis Virus Infection in Nude Mice

Nude mice which had received intraperitoneal injection of silica simultaneously with infection of mouse hepatitis virus, NuU strain, died of severe necrotic hepatitis within 2 weeks postinfection, whereas those having received no silica survived for 3 weeks or more after challenge. Silica given day 4 postinoculation had no effect. The virus titers of the liver and spleen at day 4 as well as serum interferon levels at day 2 were much higher in silica‐treated mice than those without silica treatment. At day 2 or 3 postinoculation, silica‐treated mice were found to have a considerable number of necrotic foci in the liver with some neutrophil and lymphocyte infiltration, and viral antigen was present in the cytoplasm of some hepatocytes around necrotic foci. In contrast, those without silica treatment showed only some necrotic foci with some lymphocyte infiltration. Viral antigen was detected only in a few littoral cells but not in hepatocytes. The role of macrophages in the resistance at early stage of infection in nude mice is discussed.

Effect of Mouse Hepatitis Virus Infection on “Natural Killer Cell” Activity in Nude Mice

In nude (numu) mice reared in a conventional environment, mouse hepatitis virus (MHV) has been shown to be of importance as a cause of wasting syndrome (6). We previously reported that a low-virulent strain of MHV isolated from diseased nu/nu mice (6) was capable of producing a persistent infection with hepatitis and wasting syndrome in nu/nu mice but not in their heterozygous (nul +) counterparts (17-19). Nujrru mice have been widely used for experimental transplantation of human malignant tumors (2, 12, 14), and Kyriazis et al observed that MHV infection influences human tumor cell growth in nu/nu mice (9). On the other hand, Herberman et al (3) suggested that some viral infections might enhance the activity of natural killer (NK) cells which are known to play some role in destruction of tumor cells. This communication is to describe the effects of MHV infection on the NK cell activity in nujnu mice. Male nujnu and female nul+ mice having a BALB/c background were obtained from a commercial breeder (Japan CLEA, Tokyo). The breeder colony had been tested for freedom from MHV infection by anamnestic serology with retired breeder mice (1). The mice were maintained and bred in vinyl isolators on commercial pellets (Oriental Yeast, Tokyo) and water, both sterilized by heating at 120 C for 30 min. The nu/nu and nul+ offspring were brought to a conventional environment outside the isolators at 6 to 8 weeks of age, and subjected to experimental infection. Infected animals were kept in cages covered with a barrier filter (Sankikagaku, Tokyo). The NuU strain of MHV (MHV-NuU) (6), which had been isolated in SRCDFI-DBT (DBT) cells (5) from the affected liver of a wasted numu mouse, was used at the 17th passage level in DBT cells. The culture supernatant was harvested 15 hr after inoculation and stored at -20 C. Before inoculation, the stored material was diluted with phosphate buffered saline, pH 7.2 (PBS), and 2 X 104 plaque-forming units (PFU) of the virus on DBT cells (5) were inoculated intraperitoneally (i.p.). The spleens were taken from three to six mice of each group and immersed in cold Eagles minimum essential medium (MEM) (Eiken, Tokyo). The resulting spleen cell suspension was then subjected to hypotonic shock in 0.83% NH4Cl in