John Hotchin

Host genetics and the behavioral sequelae to herpes encephalitis in mice

The effects of intracerebral infection with herpes simplex virus on the subsequent behavior of two strains of mice were examined. Infected Nya:NYLAR mice were hyperactive and did not show any deficits in the acquisition or reversal of a spatial learning task. In contrast, infected Nya:(SW) mice were hypoactive and made more errors than controls during both phases of the learning tasks. These differences in the nature of the sequelae to infection were related to an overall higher virus titer in the brains of Nya:(SW) mice, an effect particularly marked in the cerebral hemispheres. The results suggest that herpes encephalitis may produce a variety of behavioral syndromes, depending in part on the genetic background of the host. The relevance of these findings to clinical disorders produced by viral infection is discussed.

Electron microscopical aspects of hemadsorption in tissue cultures infected with influenza virus

Abstract Adsorption of guinea pig erythrocytes to monkey kidney cells in tissue culture infected with influenza virus was found by electron microscopy to occur by two processes. In one, the red cells were attached to virus filaments protruding from the host cell cytoplasmic membrane, and the red cell and host cell were separated by a distance of up to 1μ. This type of attachment is similar to that seen in hemagglutination. In the other, there was direct and close binding of the erythrocytes to the infected monkey kidney cell in the absence of detectable virus filaments or particles. The significance of the finding of an apparent change in the immunologically specific structure of the surface of the host cell following infection by influenza virus is discussed.

Survival of Micro-Organisms in Space

Dried suspensions ofPenicillium roqueforti Thom, Coliphage T-1,Bacillus subtilis and tobacco mosaic virus were exposed to space on board the Gemini-IX-A and XII earth satellites and the Agena-VIII space rocket. All micro-organisms tested survived the direct exposure during the Gemini-IX-A experiment. In the Gemini-XII experiment only the T-1 phage survived the direct exposure. The survival was influenced by the suspending medium and depended on the species of the microorganism. After four months of space flight on the Agena-VIII space rocket surviving fractions between 2×10−3 and 1.0 were found in the unopened flight container. However, micro-organisms exposed on the cover of the container during this period were completely inactivated. Shielding against solar ultraviolet radiation during flight resulted in survival of micro-organisms exceeding to that of the transport controls, and the survival was considered complete.Sterile methylcellulose collection surfaces were exposed to space on board the Gemini-IX-A and XII satellites in an attempt to collect viable micro-organisms in space. None of the collection surfaces yielded viable micro-organisms.

Factors affecting the Induction of Persistent Tolerant Infection of Newborn Mice with Lymphocytic Choriomeningitis.

Abstract Persistent tolerant infections (PTI) with lymphocytic choriomeningitis (LCM) virus were initiated in mice by inoculation during the first few days after birth. Tolerance resulted in all animals which did not die during the first few weeks following inoculation. Thus, the effects of various variables upon the incidence of tolerance were determined by measuring the mortality following inoculation. It was found that the passage history of the virus used exerted a marked effect upon the incidence of mortality of newborn mice following intracerebral inoculation. Previous intracerebral passage of the virus inoculum resulted in high mortality and almost no surviving tolerant animals, whereas repeated intraperitoneal passage produced a virus which caused a very high incidence of tolerance. Inoculum dose did not markedly affect the induction of tolerance although in general high doses of virus caused lower mortality (greater tolerance). Intracerebral inoculation produced a greater proportion of tolerant animals than intraperitoneal inoculation. Viruses with a high ability to induce tolerance were described as docile, whereas strains with poor tolerance-inducing capacity but causing high mortality were described as aggressive in terms of their ability to cause immunological conflict and death of the host. The bearing of these findings on general virology with reference to the choice of strains used in experimental research is discussed.

The production of focal herpes encephalitis in mice by stereotaxic inoculation of virus: Anatomical and behavioral effects

A low virulence strain of herpes simplex type 1 was microinjected into the hippocampus of BALB/c mice. Intense replication of virus at the inoculum site was followed by spread of viral antigen to the afferent connections of the hippocampus. Surviving animals showed focal damage of limbic structures and specific behavioral abnormalities generally consistent with hippocampal damage. This procedure thus produces an animal model which more closely resembles human herpes encephalitis than those previously reported.

Quantitative applications of fluorescent antibody technique to influenza-virus-infected cell cultures

Abstract Tissue cultures of chick embryo cells, the FL strain of human amnion cells, and calf kidney cells, all infected with two strains of influenza virus (Asian and PR8) were studied by the fluorescent antibody technique. A quantitative method was used employing a differential count of fluorescent cells. The maximum yield of fluorescent cells was obtained with an adsorption period of 1 hour. The number of fluorescent cells could be halved by addition of antiserum 30 minutes after exposure to virus, whereas after 4 hours antiserum had no effect. The chick embryo cultures showed the highest proportion of fluorescent cells. Ninety per cent of these cells could be made to fluoresce with an EID 50 : cell ratio of 20. Infective Asian influenza virus was released from infected calf kidney cells but not from infected chick and FL cells. Evidence is presented that this technique can be used for the rapid assay of viruses.

Slow Virus Kidney Disease of Mice

Preliminary observations based on organ weight differential, renal function, and glomerular lesions in mice infected neonatally with lymphocytic choriomeningitis indicate the presence of a slow virus-induced kidney disease of mice. This condition is accompanied by a marked decrease in the size of the kidneys, with progressive diminution of renal function, as shown by measurements of creatinine and urea clearance.

TOLERANCE TO LYMPHOCYTIC CHORIOMENINGITIS VIRUS

The behavior of LCM virus in mice forms one of the two pillars that support the edifice of acquired immunological tolerance in biology. Tolerance, when used in the medical sense, is defined as the constitutional or acquired capacity to endure, without injury, the effects of a poison or other substance. In this presentation, tolerance is taken to mean the capacity of the host to endure the presence of large quantities of virus and virus-infected tissue without rejection for prolonged periods of time. “Immunological tolerance” was used by Burnet and Fenner * to explain the lack of an immune response to the body’s own components. This concept was postulated by these authors on the basis of two previous observations: (1) Owen’s observations of chimerism in twin cattle, and ( 2 ) Traub’s results on the carriage of asymptomatic lymphocytic choriomeningitis (LCM) virus infection in congenitally infected m i ~ e . ~ ~

Host and viral genetic determinants of the behavioral effects of scrapie encephalopathy

Abstract The influence of virus and host genetics on the nature of the behavioral effects of scrapie encephalopathy were examined in two studies. In the first study the qualitative nature of the effects of the virus on open-field and Y-maze exploration were found to depend upon the host (mouse strain) genotype. In the second study these same behaviors were found to be influenced by the viral genetics. Thus qualitative effects of scrapie encephalopathy on host behavior depend upon both the viral and host genotypes.

Disappearance of Scrapie Virus from Tissues of the Mouse

Examination of newborn mice, inoculated intraperitoneally with high doses of scrapie virus, revealed that the virus could not be reisolated from their tissues after about 1 week following inoculation, until almost 1 year later. The inoculum was rapidly removed and was not detectable, although the animals became latently infected. Homogenization of whole inoculated newborn animals showed that only about 3% of virus could be recovered by the 2nd day postinoculation (p.i.). During the first 6 days p.i. the half-life of titratable scrapie was about 15 h. A further study of the rate of disappearance of clarified scrapie virus from blood after intravenous inoculation showed an even more rapid disappearance, with a half-life of 5.16 min. Prior treatment of the recipient mice with either carbon black or silica to block the reticuloendothelial system (RES) did not affect the rate of disappearance. It was concluded that the mouse possesses a very efficient means of scrapie virus removal from the blood which is not dependent upon an active RES. However, after 1 h the rate of disappearance changed dramatically; the residual virus level was very stable, with no significant drop during the next 21 h. This finding was compatible with the possibility that two forms of scrapie virus, with different removal rates, coexisted in the inoculum. Silica treatment caused a shortened scrapie incubation period.