William Horner Andrews (1887-1953)- first professor of physiology at Onderstepoort.

W H Andrews qualified as a veterinarian in London in 1908 and was recruited soon after, in 1909, by Sir Arnold Theiler to join the staff of the newly established veterinary laboratory at Onderstepoort. After initial studies on the treatment of trypanosomosis and on snake venoms he was deployed by Theiler in 1911 to start research on lamsiekte (botulism)at a field station on the farm Kaffraria near Christiana, where he met and married his wife Doris. After a stint as Captain in the SA Veterinary Corps during World War I he succeeded D T Mitchell as head of the Allerton Laboratory in 1918, where he excelled in research on toxic plants, inter alia identifying Matricaria nigellaefolia as the cause of staggers in cattle. When the Faculty of Veterinary Science was established in 1920 he was appointed as the first Professor of Physiology. After the graduation of the first class in 1924, and due to health problems, he returned to the UK, first to the Royal Veterinary College and then to the Weybridge Veterinary Laboratories of which he became Director in 1927. After his retirement in 1947 he returned to South Africa as a guest worker at Onderstepoort where he again became involved in teaching physiology when Prof. Quin unexpectedly died in 1950. Andrews died in Pretoria in 1953 and was buried in the Rebecca Street Cemetery.

History of bluetongue research at Onderstepoort.

Research on this economically important disease of ruminants, especially sheep, which had been named bluetongue by farmers in the 19th century, has been part and parcel of the activities at Onderstepoort ever since its establishment in 1908 and therefore covers a full century of the OVI's existence. In view of Onderstepoort's centenary celebration a brief overview of this research is given in terms of the historic milestones which influenced and guided global research on this and other viral diseases of animals.

The effect of a natural maedi-visna virus infection on the productivity of South African sheep.

A cohort study was conducted in order to measure the effect of the chronic indurative lymphocytic mastitis caused by the South African strain of maedi visna virus (MVV) on the pre-weaning growth of lambs born either of naturally infected or uninfected ewes kept under similar conditions. Fifty naturally infected ewes as well as another 40 from a maedi-visna-free source to be used as control animals, were purchased and kept in separate flocks which were managed in a similar way. All the ewes were of the same breed and 3-4 years old. During the adaptation period, and through the mating, pregnancy and lactation periods they were periodically monitored for the presence of MVV serum antibodies. The lambs were weighed at birth and thereafter every 2 weeks until the age of 90 days, when they were weaned. The ewes were then slaughtered, and their udders examined histologically and the number of lymphocytic follicles were counted and assessed. Although the calculated values indicated a correlation between the number of follicles in the udder and the reduction in the growth rate of the lambs, this was not statistically significant. Similarly, despite higher counts of lymphoid follicles in the udders of sero-positive ewes as compared to those that were sero-negative and the lower ewe productivity indexes in infected ewes, no statistically significant differences were found in the indexes of ewes in different follicle categories.

The role of veterinary research laboratories in the provision of veterinary services.

Veterinary research laboratories play an essential role in the provision of veterinary services in most countries. These laboratories are the source of new knowledge, innovative ideas and improved technology for the surveillance, prevention and control of animal diseases. In addition, many laboratories provide diagnostic and other services. To ensure the optimal integration of various veterinary activities, administrators must understand the functions and constraints of research laboratories. Therefore, a brief discussion is presented of the following: organisational structures methods for developing research programmes outputs of research scientists and how these are measured the management of quality assurance funding of research. Optimal collaboration can only be attained by understanding the environment in which a research scientist functions and the motivational issues at stake.

Detection of Maedi-Visna virus antibodies using a single fusion transmembrane-core p25 recombinant protein ELISA and a modified receiver-operating characteristic analysis to determine cut-off values.

The core p25 and transmembrane (TM) genes of Maedi-Visna virus (MVV) were cloned individually into the pGEX-2T expression vector. Both proteins were expressed as a combined fusion protein in frame with glutathione S-transferase (GST). The purified recombinant antigens (GST-TM and GST-TM-p25) were used to develop a MVV ELISA. A preliminary assessment of the diagnostic potential of the recombinant antigens (GST-TM and GST-TM-p25) was made by testing the antigens against 46 seropositive and 46 seronegative sheep and comparing the results with a commercial p25 ELISA kit. A two-graph receiver operating characteristic (TG-ROC) analysis program was used to interpret the data. The GST-TM-p25 ELISA was more sensitive than the commercial assay which is based on the p25 antigen alone and more specific than the GST-TM ELISA.

Nucleotide sequence of the jaagsiekte retrovirus, an exogenous and endogenous type D and B retrovirus of sheep and goats.

The complete genome of the jaagsiekte sheep retrovirus (JSRV), the suspected etiological agent of ovine pulmonary carcinoma, has been cloned from viral particles secreted in lung exudates of affected animals and sequenced. The genome is 7,462 nucleotides long and exhibits a genetic organization characteristic of the type B and D oncoviruses. Comparison of the amino acid sequences of JSRV proteins with those of other retrovirus proteins and phylogenetic studies suggest that JSRV diverged from its type B and D lineage after the type B mouse mammary tumor virus but before the type D oncoviruses captured the env gene of a reticuloendotheliosislike virus. Southern blot studies show that closely related sequences are present in sheep and goat normal genomic DNA, indicating that JSRV could be endogenous in ovine and caprine species.

Isolation, identification, and partial cDNA cloning of genomic RNA of jaagsiekte retrovirus, the etiological agent of sheep pulmonary adenomatosis.

The genome of the jaagsiekte (JS) retrovirus (JSRV), the etiological agent of sheep pulmonary adenomatosis (jaagsiekte), has been identified, isolated, and partly cloned. The JSRV genome is ca. 8.7 kb long. cDNA of the genomic RNA was synthesized and cloned. A clone, JS 46.1, was isolated and characterized. It has an insert of 2.1 kb which hybridizes to the same 8.7-kb RNA in all the JSRV-infected sheep lung washes tested but does not hybridize to maedi-visna virus, a sheep lentivirus often found coinfecting JSRV-infected lungs. Comparison of the amino acid sequence encoded by JS 46.1 with those encoded by other retroviruses revealed that JSRV has homology to the type D and B oncoviruses and to human endogenous retrovirus.

Some characteristics of a retrovirus isolated from transformed bovine cells.

A novel retrovirus has been isolated from bovine cells transformed after cocultivation with leukocytes from an animal suffering from sheep-associated bovine malignant catarrhal fever. Morphologically and in its morphogenesis the virus resembles the type D Mason-Pfizer monkey virus (MPMV) as well as the ovine jaagsiekte retrovirus (JSRV). It is also serologically related to these two viruses, whereas a relationship to other known bovine retroviruses was not detected. However, its density of 1.16 g/ml in sucrose and the preference of its reverse transcriptase for manganese ions are closer to the characteristics of type C retroviruses. Unsuccessful attempts at transmission suggest that the virus may be defective in some function affecting its infectivity.

The possible involvement of immunosuppression caused by a lentivirus in the aetiology of jaagsiekte and pasteurellosis in sheep.

A South African isolate of ovine lentivirus was shown to cause a mild immunosuppression in sheep, reflected by a reduced delayed hypersensitivity reaction. This effect, measured in terms of skin swelling after intradermal inoculation with tuberculin, showed a positive linear relationship with the latency period before the appearance of jaagsiekte symptoms in animals co-infected with JSRV, as well as with the activity of monocytes. In a parallel study, increased susceptibility of lentivirus-infected sheep to infection with Pasteurella haemolytica was demonstrated. It is concluded that the lentivirus may play an enhancing role in both viral and bacterial infections of sheep by compromising the host's cellular immune response.

Experimental transmission of jaagsiekte (ovine pulmonary adenomatosis) to goats.

Jaagsiekte was successfully transmitted to at least 2 out of 6 goats inoculated intratracheally with partially purified jaagsiekte retrovirus. Multiple, small, well circumscribed nodules found in the lungs consisted of typical papilliform proliferations of neoplastic Type II epithelial cells. Histological evidence of a mild interstitial pneumonia in 4 of the experimental animals can probably be attributed to a contaminating lentivirus in the jaagsiekte retrovirus preparation, as suggested by the seroconversion of the animals.

Demonstration of growth-inhibitory as well as growth-stimulatory factors in medium conditioned by lung lavage cells stimulated with a chemotactic factor secreted by jaagsiekte tumour cells.

Both growth-inhibitory and growth-stimulatory factors were detected in vitro in medium from chemotactically stimulated cultures of lung lavage cells. The macrophage component of the lavage cells was found to produce a growth stimulatory factor that was replaced by a growth inhibitory factor following chemotactic factor stimulation.

Characteristics of a novel lentivirus derived from South African sheep with pulmonary adenocarcinoma (jaagsiekte).

A novel lentivirus was isolated from South African sheep with experimentally transmitted lung adenocarcinoma. Similar to visna virus and caprine arthritis encephalitis virus, this new strain induced cytopathic effects on ovine plexus choroid cultures. In contrast to a recent Israeli isolate from sheep with adenocarcinoma, the South African lentivirus could not transform fibroblast cultures. The antigenic relatedness between the new isolate and visna virus was assessed by immunoprecipitation of radiolabeled viral proteins, using monospecific antisera against visna virus proteins. The results indicate that the new virus contains four major structural proteins of sizes similar to those of visna virus (i.e., gp135, p30, p16, and p14) and have some common antigenic determinants (about 90% in the major core antigen p30). However, the nucleotidic sequences of the novel lentivirus were found to be only 16.5 to 27.4% homologous to visna virus and 8.3 to 15% homologous to caprine arthritis encephalitis virus, by means of liquid hybridization under stringent conditions. The genetic divergence indicated by this last result was confirmed by the dissimilar restriction endonuclease cleavage map of the new virus in comparison to those of visna virus and three caprine arthritis encephalitis virus strains. The demonstration of a third type of ovine lentivirus supports the concept of an important genetic variation among the lentiviruses infecting one animal species.

Production of a macrophage chemotactic factor by cultured jaagsiekte tumour cells.

The increase of alveolar macrophages in jaagsiekte sheep lungs is not caused by excessive surfactant production but is due to a chemotactic factor secreted by the tumor cells. This factor has a molecular mass in the region of 13 kilodaltons, is stable at 56 degrees C but labile at 100 degrees C and, being sensitive to proteases, indicates that it is a small protein molecule.

The localization of a Mason-Pfizer monkey virus-related antigen in jaagsiekte tumour tissue and cell lines.

Mason-Pfizer monkey virus-related antigen was detected in 3 out of 5 jaagsiekte lungs examined using a direct immunoperoxidase staining technique with anti-MPMV p27 serum. Most of the antigen was localized in the alveolar lumina of the lesions. The reaction was further characterised on immune blots and found to involve a protein with a molecular mass of 29 000 daltons (JSRV p29). JSRV p29 antigen was also detected in 2 jaagsiekte cell lines.

Isolation and identification of a South African lentivirus from jaagsiekte lungs.

In the course of attempts to grow the jaagsiekte retrovirus in cell culture, a typical lentivirus was isolated for the first time in South Africa from adenomatous lungs. Morphologically the virus could not be distinguished from other lentiviruses, but serologically it was shown to be more closely related to visna virus than to caprine arthritis-encephalitis virus. However, a preliminary restriction enzyme analysis of the linear proviral DNA of this new lentivirus (SA-DMVV) revealed that it is significantly district from visna virus and CAEV and therefore may represent a third type of lentivirus. Antibodies to the virus were demonstrated in a number of sheep in various parts of the country, but a direct link to a disease condition was not found. Attempts to produce lung lesions by intratracheal injection of the virus have been unsuccessful to date but a transient arthritis was produced by intraarticular inoculation. Viral replication seems to be enhanced in jaagsiekte lungs.

Biotechnology, viral oncogenesis and jaagsiekte.

A brief description is given of the discovery of retroviral and cellular oncogenes and of their putative role in oncogenesis. Attempts to apply the biotechnological techniques that were so successful in the study of other retroviruses to the newly-discovered jaagsiekte retrovirus are briefly reviewed.