Simian Strain Research Articles

The Use of an Immunofluorescence Technique for the Determination of Antibodies to Cytomegalovirus Strains in Human Sera

Abstract An immunofluorescence technique was used to investigate antigenic heterogeneity among cytomegalovirus (CMV) strains. Twelve strains of human CMV were examined by titration with their homologous human sera. The strains were selected to reflect a range of geographic origin, site and year of recovery, age and clinical disease of the host. Antigens from CMV strains AD 169 and Davis, a simian CMV strain, herpes simplex and varicella-zoster (VZ) viruses were included. On the basis of this initial study, the human CMV strains studied appeared to fall into three groups. Two strains recovered in Taiwan formed one distinct group. Other strains from Taiwan, however, were not found to give the same reaction pattern, so the difference did not appear to be due strictly to geographic origin. UW-1 and UW-2 strains from neonatal infections and another Seattle strain from a case of recurrent parotitis constituted a second group. The remaining strains fell into an intermediate group, distinct from the Taiwan strains. No similar differentiation was found in complement-fixation (CF) tests with the same sera and antigens. Human CMV strains did not appear to cross-react in the immunofluorescence test with other members of the herpesvirus group, including the CMV strain of simian origin. The specificity of this technique warrants its use as a diagnostic tool for virus identification, since most of the human CMV strains employed as antigens detected antibody in any of the sera tested. Although the CF test appeared to be species-specific for cytomegaloviruses, and hence may have the most general utility for antibody detection, the greater sensitivity of the fluorescent antibody (FA) technique warrants its use for detecting small amounts of antibody when the correct antigen can be ascertained.

Differentiation of Cross-Reacting Simian Cytomegalovirus Strains by Late 19S Rabbit Neutralizing Antibodies

Abstract The results of studies reported previously (1–3) demonstrated heterogeneity in the neutralizing properties of early (7-day) and late (hyperimmune) 7S and 19S antibodies prepared in rabbits against human herpes simplex virus (HSV) and the simian herpesvirus SA8. In the case of the late antibodies, we showed reciprocal cross-neutralization with the 7S antibodies, whereas neutralization by the 19S antibodies was limited essentially to the immunizing virus (3). Recent studies in this laboratory have been concerned with determining antigenic relationships between cytomegalovirus (CMV) strains using late immune rabbit sera (4). Evidence is presented here that the properties of late 7S and 19S rabbit antibodies prepared against simian CMV strains are similar to those reported previously for late 7S and 19S anti-HSV and anti-SA8 antibodies with respect to their specificity for the immunizing virus. Three simian CMV strains were employed. Strain SA6 was isolated from a naturally infected vervet monkey (5), and strains CV-207 and CV-209 were isolated from African green monkeys which had been inoculated with human CMV (6).

Cytomegaloviruses as Common Adventitious Contaminants in Primary African Green Monkey Kidney Cell Cultures

Twenty-seven of fifty-two lots of primary African green monkey (AGM) kidney cell cultures were found to contain cytomegalovirus (CMV). The cell cultures, all derived from apparently healthy animals, required long incubation periods before CMV could be detected. Less than half the contaminated cultures showed cytopathic effects (CPE) before 4 weeks. About one-fifth of the contaminated cultures failed to show CPE during a 40-day observation period; CMV was initially recognized in these cultures by fluorescence microscopy. Fluorescence and electron microscopy of CMV-infected cells revealed highly distinctive nuclear inclusions. All virus strains tested showed typical focal CPE on monolayers of WI-38 cells after 5 days. Nearly all AGM sera tested contained complement-fixing antibody against several simian CMV strains. Substantial levels of neutralizing antibody against one CMV strain were present in AGM sera tested. Isolation and serological data indicate that CMV is widely distributed as a latent infection among apparently healthy African green monkeys. This wide distribution in well-conditioned monkeys might be considered when the significance of herpes-like viruses in primate cells is interpreted. Simian CMV-human cell interactions are of interest because of the well-known association of herpesviruses with oncogenic processes and because simian CMV strains replicate slowly in human cells.

Preparation of Rabbit Immune Serum with Neutralizing Activity against a Simian Cytomegalovirus (SA6)

Abstract Neutralization studies with human and simian cytomegaloviruses (CMV) are presently limited to sera obtained from naturally infected hosts or from monkeys immunized with specific CMV strains (1–3). The unavailability of reference antisera prepared in non-primate hosts raises the possibility that neutralization of human or simian CMV strains by human and monkey sera may result from a heterotypic response between the CMV strain under test and antibody directed against an inter- or intra-species cross-reacting virus. Cross-neutralization for example, has been reported between Herpesvirus hominis (herpes simplex) and Herpesvirus simiae (B-virus) (4, 5), and between Herpesvirus hominis and SA8 virus (6) isolated from vervet monkeys (7). The use of immune sera from non-primate hosts should minimize, although not completely exclude, the possibility of a heterotypic antibody response in serologic studies with human and simian CMV strains. This report concerns the preparation of antiserum in rabbits with neutralizing activity against a simian CMV (SA6) isolated from vervet monkeys (7).

Morphology of tumors induced in hamsters by simian adenoviruses.

AbstractSubcutaneous hamster tumors induced by Simian adenovirus SA7, strains C8, B105 and C626, were found to be poorly differentiated sarcomas having morphological features which distinguish them from tumors induced at the same site by papovaviruses and the Rous sarcoma virus. In general, the adenovirus‐induced tumors were morphologically alike, C8‐induced sarcomas showing some differences. Tumors induced by this strain in the subcutaneous tissue, muscles, peritoneum and mediastinum were morphologically identical. Tumors found in the brain were mainly malignant ependymomas and choroid plexus carcinomas, generally originating in neuroectoderm.The oncogenicity of adenovirus SA7 (C8) in meso‐ and ectodermal cells has thus been demonstrated.

Spectrum of Human Cytomegalovirus Complement-Fixing Antigens

Summary The antigenic properties of two strains of monkey cytomegalovirus (CMV) were analyzed and compared with several human CMV strains. Analysis of the strains was made possible by utilization of selective cross-reactive sera obtained from African green monkeys recently taken into captivity. A uni-directional cross of complement-fixing (CF) reactivity was demonstrated in that certain monkey sera reacted with both monkey and some, but not all, human CMV strains; however, human sera reacted only with human CMV. In contrast, the serum neutralization reactions with these two systems were species specific; monkey sera neutralized only simian CMV strains and human sera neutralized only human CMV strains. Monkey sera which contained CF antibodies against simian CMV gave a spectrum of reactivity when tested with five different strains of human CMV. About 90% of these monkey sera reacted with human CMV strain AD-169 but none reacted with strain C-87. Approximately 50% of these sera reacted with strains BC-13 and L-38E and 25% reacted weakly with the Davis strain. It was concluded that the various human CMV strains possess overlapping mosaics of CF antigens which can be differentiated with sera obtained from monkeys naturally infected with simian CMV.

Attempts to Propagate Murine Poliomyelitis Virus on Various Intestinal Bacteria and Protozoa.

ConclusionsPropagation of human or simian strains of poliomyelitis virus in any kind of culture medium is extremely difficult whereas certain murine strains will grow well in tissue culture containing embryonic mouse brain. A number of enteric bacteria and protozoa as well as some highly differentiated non-intestinal protozoa were examined for their ability to permit propagation of MM murine poliomyelitis virus in culture. No evidence of viral propagation was found as determined by mouse inoculation. The data do not encourage the assumption that neu-rotropic poliomyelitis virus in stool or sewage may be maintained in symbiosis with free living microbial cells. However the limited extent of this work does not exclude the possibility that experiments with other marine or faecal organisms under different experimental conditions might be more successful.

STUDIES IN RODENT POLIOMYELITIS

1. Attempts to separate by processes of physical segregation, i.e. ultrafiltration, ultracentrifugation, or dialysis, from live SK murine poliomyelitis virus a non-pathogenic agent capable of interfering with simian poliomyelitis virus were unsuccessful. Neither was it possible to convert live SK murine virus into a non-pathogenic interfering agent by processes of chemical inactivation, i.e., phenolization or formalinization. 2. Preparations of SK murine virus, which had been markedly attenuated by ultraviolet irradiation, gave evidence of having retained some interfering power in rhesus monkeys. 3. MM murine poliomyelitis virus interfered, both in mixture tests and by peripheral administration, with two simian strains of poliomyelitis virus. With adequate amounts, distinct protective effects could be obtained in rhesus monkeys which had received murine virus (animal passage or tissue culture virus) up to 48 hours after intracerebral infection with simian poliomyelitis virus. 4. Theiler's virus of spontaneous mouse encephalomyelitis, when tested in mixture with simian poliomyelitis virus, gave some evidence of irregular and low grade interference. Interference could not be shown conclusively in experiments to prevent poliomyelitic infection or to modify its effects. 5. The nature of the interfering agent present in murine virus is discussed.