Paul Kamitsuka

Primary sites of virus multiplication following intramuscular inoculation of poliomyelitis virus in cynomolgus monkeys.

Abstract The intramuscular inoculation of a virulent type 1 poliomyelitis virus was used to delineate primary sites of virus multiplication in cynomolgus monkeys. The virus disappeared insofar as it was not detected in tissues examined for a period of about 30 hours. Virus reappeared first in skeletal muscle at the site of inoculation. The evidence indicated multiplication of virus in cellular constituents in the muscle mass. Shortly thereafter virus appeared in collateral lymph nodes, and after a further brief interval in the blood stream. After onset of viremia, virus was widely distributed in neural and extraneural tissues.

Experimental Infections with Coxsackie Viruses. I. Studies on Virulence and Pathogenesis in Cynomolgus Monkeys.

Eighty-seven monkeys were inoculated by 4 different routes with 7 strains of Coxsackie virus. The majority of the monkeys (84 per cent) developed evidence of infection adduced either by development of antibodies, occurrence of viremia or presence of characteristic anatomical lesions in CNS tissues. While the clinical characteristics differed between strains the general nature of the infection was similar for each virus. Twenty-nine monkeys developed paralysis, usually mild and transient, occasionally severe leading to death. Thirty-seven monkeys developed viremia. Higher infection rates were usually obtained after parenteral than after oral inoculation; these rates varied for different viruses. Specific lesions associated with invasion of CNS by virus were obtained in a large fraction of monkeys sacrificed before challenge with type 1 poliovirus. Myocarditis was found in three, pericarditis in two, and pancreatitis in two monkeys. Most monkeys on recovering from infection by Coxsackie viruses were not spared the risk of paralysis with type 1 poliovirus; however, some monkeys may have been spared paralytic poliomyelitis following infection with Group B, types 4 and 5 Coxsackie viruses.Nine cynomolgus monkeys were inoculated intravascularly with Group B, type 4 (Edwards strain) Coxsackie virus. Viremia developed in 6 monkeys by the 2nd day, but was not detected thereafter. B4 virus was recovered in CSF obtained from 2 monkeys. The specific antibody responses were equivocal for 8 monkeys; all showed a slight rise in antibody levels; only one monkey surviving 28 days had an unequivocal antibody response.

Further observations on the widespread distribution of poliomyelitis virus in body tissues following intramuscular inoculation of cynomolgus monkeys.

Abstract Studies made on the distribution of poliomyelitis virus in regional lymph nodes obtained from fatal human cases indicated that virus was distributed widely in extravascular tissue compartments during the preparalytic period of infection. Further evidence in support of the assumption of a widespread distribution of poliomyelitis virus early in the infectious period was obtained experimentally in cynomolgus monkeys inoculated with the Brunhilde (type I) strain of poliomyelitis virus.

Studies on the pathogenesis of monkey pox. 3. Histopathological lesions and sites of immunofluorescence.

The principal histologic features of monkey pox are cellular proliferation, degeneration, necrosis and inflammation. The major organ-systems affected are skin and mucous membranes, spleen, tonsils, lymph nodes, testis and ovary. Organs less frequently affected are kidney and pancreas. Focal accumulations of antigen were regularly revealed by fluorescent-antibody staining in tissues showing foci of necrosis, and yielding large concentrations of virus. Evidence is presented in support of specific viral injury. The pathogenesis of monkey pox is similar to other mammalian pox-infections and close particularly to variola in human beings.

Studies on the pathogenesis of monkey pox. II. Dose-response and virus dispersion.

Monkey pox virus (MPV), titrated intramuscularly in cynomolgus monkeys provided a 50 per cent infectivity endpoint of 10−5.8. All infected animals developed monkey pox. Three of 4 sentinel control monkeys developed monkey pox; one experienced subclinical infection. Viremia intervenes between the 4th and 7th days, and may persist for 4 or 5 days post-eruption, even after appearance of HI antibodies. MPV multiplies in the substance of the inoculated muscle. During the pre-eruptive stage of infection this virus is detected earliest in tonsil and spleen, and shortly thereafter in bone marrow and regional lymph nodes. During the early post-eruptive period, in addition to large concentrations of MPV in these same tissues, the virus is regularly found in cutaneous lesions, some-what less regularly in kidney, and very much less regularly in other tissues. Specific antibodies are raised during infection; HI antibodies are less enduring than CF or neutralizing antibodies. Monkeys convalescent from MPV are immune to challenge with vaccinia, but are fully susceptible to Yaba tumor virus.

The pathogenesis of poliomyelitis. Sites of multiplication of poliovirus in cynomolgus monkeys after alimentary infection

The P 1549 (antigenic type 1) strain of poliovirus was administered by gavage to cynomolgus monkeys in order to obtain additional information on primary sites of multiplication of poliovirus. The first sites of virus multiplication were in tissues of the alimentary tract, principally in the oropharynx, and possibly in the ileum. During the early period in pathogenesis poliovirus was found also in lymph nodes collateral to these alimentary sites of multiplication. As early as 24 hours after detection of poliovirus in these tissues low concentrations of virus were detected in the blood; the concentration of virus in the blood rose gradually to reach maximal levels within 48 to 96 hours; thereafter, the concentration gradually fell until no further evidence of viremia was obtained by the 10 th day after infection. When the viremia was approaching, or had reached maximal levels poliovirus was distributed widely in all 46 tissues examined for its presence. Near the end of the period of viremia specific neutralizing antibodies were also found in the blood.

Yaba Tumor Virus. I. Studies on Pathogenesis and Immunity

Summary Tumor development and CF antibody responses of monkeys inoculated s.c. and i.v. with various dilutions of Yaba tumor virus were investigated. Tumors developed at different times and at different sites with CF antibodies appearing soon after the development of tumors and attaining final CF titers comparable in all inoculated animals. No antigenic relationship between Yaba virus and monkey pox viruses was found by in vivo challenge, or between Yaba, monkey pox, and vaccinia virus by cross CF and HI tests. The development of viral antigen(s) in tumor cells removed from infected monkeys at weekly intervals was monitored by the FA technique and CF test. Although the FA technique detected the viral antigen earlier, both procedures were equally effective for detection of antigen in tumors removed 4 or more weeks postinfection.

On the Alleged Antigenic Relation between ECHO Virus Types 29 and 32.

Discussion and summary The data presented here indicate clearly that the previously reported antigenic relationship between ECHO types 29 and 32 was the result of working with a mixture of the viruses in question. No antigenic relationship between these types was detected by tube neutralization, plaque-reduction, or hemagglutination-inhibition tests when “purified” reagents were employed.