Nicola M. Tauraso

Virus Isolations from Human Cases of Hemorrhagic Fever in Bolivia

Summary Five serologically similar virus strains were recovered in San Joaquin, Bolivia, in 1963 from humans suffering from a newly recognized febrile disease with hemor-rhagic manifestations. Three isolates were from splenic tissue obtained at autopsy and 2 from blood specimens taken from acutely ill patients. The prototype strain (Carvallo) was pathogenic for newborn mice and hamsters, produced cytopathic effects in WI-26 cell cultures and plaques in MA-111 cell cultures, was inactivated by chloroform, and was estimated to be 180 mμ or less in size. It was nearly indistinguishable from Junin and Tacaribe viruses by complement fixation test, but completely distinct from these agents by neutralization test. It is proposed that these strains collectively be named Ma-chupo Virus. The authors are indebted to Drs. Luis Valverde Ch. and Hugo Garron, Hemorrhagic Fever Commission, Ministry of Health, Bolivia, to Dr. Conrad Yunker, Rocky Mountain Laboratory of this Institute, and to Dr. J. P. Woodall, East African Medical Research Institute, Entebbe, Uganda, for their unstinting help in the work in San Joaquin. Mr. John Vogel, Mr. Angel Muñoz, Miss Elizabeth Earley, Mr. Fred Mitchell, Miss Darlene Del Nero and Mr. G. R. Rankin contributed valuable technical assistance.

PROTECTION AGAINST JUNIN VIRUS BY IMMUNIZATION WITH LIVE TACARIBE VIRUS.

Summary Adult guinea pigs immunized with the live Tacaribe virus are able to resist challenge with a large dose of Junin virus to which they are normally susceptible. Sera from the Tacaribe virus-immunized guinea pigs contain abundant homologous antibody demonstrable by both complement-fixation and plaque neutralization tests. The complement-fixing antibody titers of these sera with the heterologous Junin antigen are moderately high. However, the amount of antibody determined by the plaque neutralization test with Junin virus is negligible.

Epizootic of Simian Haemorrhagic Fever

Two epizootics of simian haemorrhagic fever (SHF) have been reported among quarantined Indian rhesus monkeys (Macaca mulatta). The first outbreak occurred in July 1964 at the Sukhumi Institute of Experimental Pathology and Therapy, USSR1,2; the second occurred in October 1964 at the US National Institutes of Health (NIH) quarantine colony3,4. The virus causing the NIH epizootic was isolated in cell culture and characterized5. Although the Soviet workers showed that the disease could be transmitted from monkey to monkey, they have not yet isolated the causative agent in either cell culture or small laboratory animals. This report describes the isolation in cell culture of the virus causing the Sukhumi epizootic and the serological relationship between the viruses causing the Sukhumi and NIH outbreaks.

The effect of altered immune reactivity on experimental measles encephalitis in rats.

Rats of the Lewis strain, infected intracerebrally with a neuro-adapted strain of measles virus, developed a non-lethal encephalitis persisting throughout the 31 days of observation. Specific antibodies, but not delayed hypersensitivity, developed in the infected animals. Histology revealed a chronic proliferative form of encephalitis localized predominately in the white matter. Stimulation of hypersensitivity with measles antigen in Freunds complete adjuvant completely eliminated encephalitic lesions in animals examined 31 days after intracerebral infection. The possibility that delayed hypersensitivity is an important factor in the immune defense against neurotropic measles infection is considered.

Yellow Fever Vaccine. IV. Reactogenicity and Antibody Response in Volunteers Inoculated With a Vaccine Free From Contaminating Avian Leukosis Viruses

Summary Removal of avian leukosis viruses (ALV) which have contaminated the yellow fever (YF) 17D vaccine since its development in the middle 1940s, had no effect upon the reactogenicity and antigenicity of this vaccine in man. From results of plaque neutralization (PN) tests, the high degree of antigenicity of the 17D vaccine was confirmed. Preexisting yellow fever antibody appeared to interfere with the antibody response to YF vaccine. Administration of YF vaccine did elicit antibodies capable of cross-reacting with West Nile, and less so with Langat, arbovirus antigens.

Avian leukosis antibody response in individuals given chicken embryo derived vaccines.

Under natural conditions, avian leukosis viruses (ALV) produce in chickens a variety of malignant disorders, manifested as solid invasive tumors, lymphomatosis, myeloblastosis, etc. As these agents are ubiquitous in conventional chicken flocks and are transmitted vertically from hen to egg, virtually all vaccines derived from conventional eggs are contaminated with ALV (1—4). Experimentally, some strains of Rous sarcoma virus (RSV) have produced tumors in nonavian species (5), including nonhuman primates (6). Because of this, the question of the potential oncogenicity of ALV to humans arises. There have been isolated reports of serologic surveys of ALV antibody in man (2, 3). These previous studies were limited to the detection of neutralizing antibody to the Bryan strain of RSV, a test only sensitive to subgroup A avian leukosis viruses. We have, therefore, examined multiple sera from individuals inoculated with ALV-contaminated vaccines for the presence of antibody by employing the broadly reacting COFAL (7) and the highly sensitive indirect immunofluorescence (FAB) tests. The COFAL test is able to detect antibody to ALV of any subgroup. In the FAB test, subgroup A, B, and C antigens were employed to broaden the antigenic spectrum to cover the three largest ALV subgroups. Neutralization tests were performed on some sera. The results of these studies constitute this report. Materials and Methods. Vaccines. All ALV-contaminated vaccines were produced in chicken embryos derived from conventional flocks and were known to be contaminated with ALV. The ALV-free yellow fever vaccine (YFV) was prepared in ALV-free eggs from seed lots also free from ALV (4). Sera. Pre- and postimmunization serum samples were obtained from the following individuals inoculated with ALV-contaminated vaccines: 35 volunteers who received formalin-inactivated influenza vaccine in single or multiple doses; 15 inoculated with formalin-inactivated epidemic typhus vaccine; 15 who were given live attenuated measles vaccine; 15 who received conventional 17D YFV; and 15 who were given live smallpox vaccine.

Yellow fever vaccine. I. Development of a vaccine seed free from contaminating avian leukosis viruses.

Summary An avian leukosis virus (ALV) free primary yellow fever vaccine seed has been developed by ridding the 17D virus vaccine seed of its ALV contaminant. By differential filtration through Millipore membrane filters of different pore sizes, yellow fever virus was separated from its contaminant by physical means. The ALV could not be detected in the new primary and secondary vaccine seeds by RIF, COFAL, and FAB tests.

Identification of two plaque variants of Guaroa virus

The prototype CoH35211 strain of Guaroa virus contained 2 different plaque populations when French or Mann agarose were used for solidifying the overlay medium. The pl1L (large) and p12S (small) plaque variants were similar with respect to pathogenicity for suckling mice (SM), titers achieved in SM brains after intracranial inoculation and time of appearance of plaques under agarose overlay. The prototype CoH35211 strain and the 2 plaque variants were indistinguishable by complement-fixation and plaque-neutralization tests. However, the 2 plaque variants differed with respect to plaque size and sensitivity to the inhibitory effects of sulfated agar polysaccharides. The only different serological relationship was a “one-way” cross-reaction between p12S antibody and California encephalitis and Tahyna viruses by plaque-neutralization test.

Foamy virus serotypes 1 and 2 in rhesus monkey tissues.

The isolation and serologic identification by cross neutralization tests showed the presence of simian foamy virus serotypes 1 and 2 in primary rhesus monkey brain, spleen, and kidney cell cultures. The frequency of isolation of foamy viruses from brain and spleen cell cultures was 86% and from kidney cell cultures it was 36%. In primary spleen cell cultures 50% of the foamy virus isolates were type 2. Of the 14 animals from which foamy virus was isolated, only 4 demonstrated serum neutralizing antibody to the homologous serotype. The cytopathology of foamy viruses in the primary cell cultures is described.

Properties of a measles virus neuropathic for rhesus monkeys

A highly hamster brain adapted strain of measles virus, capable of producing encephalitis in monkeys, inoculated into Vero cell cultures replicated in a suppressed growth cycle. No virus was released into the medium and the infected cells lacked specific virus determinants for hemadsorption. A complete replicative cycle was achieved after six subcultures of Vero cells and was accompanied by a partial drop in neurovirulence. However, hamster neuropathogenicity persisted throughout 26 Vero passages and was markedly higher than in non-brain passaged strains. High neurovirulence was associated with pronounced giant cell cytopathic effect and thermolability. On continuous passage these three properties dissociated at different rates indicating that they are independent properties of measles virus. The importance of their coincidence for the initiation of an encephalitic process in the brain of primates is stressed.