Page 16 - VHSA - Onderstepoort 100 Years - Part 3

OND
ERSTEPOORT 100
Els was a graduate in physics who established an electron microscopy unit within the section and was responsible for most of the research on the ultrastructural morphology of the viruses studied over the next two decades.
of hard work were spent on elucidating the relationships and functions of the various nucleic acid and protein components. Also of special interest were the mechanisms involved in the
Excellent technical support was provided by J.H. (Johan) Broekman and P.A.M. (Flip) Wege who were experienced in cell culture technology and who established the routine production of virus which was essential for all molecular studies. Broekman was later promoted to the vaccine factory (OBP) where he eventually retired as manager.
“A first breakthrough in bluetongue virus research came when sufficient virus had been purified to isolate its genetic material and determine whether it was DNA or RNA.”
replication of the virus and the effect these processes have on the metabolism of the host cell. The rationale behind the work was that a better understanding of a virus and its multiplication strategy could lead to better control of the disease it causes. At this time many new techniques were being developed in molecular biology, notably those for sequencing nucleic acids, for cloning genomes in suitable vectors and for the construction of recombinant viruses. These new techniques, which collectively became known as ‘biotechnology’, were increasingly applied in the research on
A first breakthrough in bluetongue virus
research came when sufficient virus had
been purified to isolate its genetic material
and determine whether it was DNA or
RNA. At the time all viruses that had been
examined contained either single- or double-stranded DNA, or single-stranded RNA. This complied with the so-called central dogma of molecular genetics, which stated that genetic in- formation resides in ds-DNA which is transcribed into single- stranded messenger RNA which in turn is translated into protein. The results obtained with BTV nucleic acid, however, were contradictory and confusing.
practical disease problems.
H. (Henk) Huismans, who joined the group in 1966, was
to play a major role in using the new techniques for the development of recombinant vaccines and improved diag- nostic methods. After spending two years at Duke University in the USA, working on reoviruses, he was appointed as head
of the Biochemistry Section in 1977 when Reinach retired. It was decided to terminate all the traditional analytical work in the section, which had become obsolete, and transfer the orbivirus work to Biochemistry. Verwoerd remained as head of Molecular Biology but switched to research on cancer viruses with the emphasis on jaagsiekte, a disease first described in South Africa in the 19th century but of unknown aetiology.
Biochemistry Section
transformed
Under the leadership of Huismans the research on BTV and AHSV remained at the forefront in international terms. Initially he studied protein synthesis in BTV-infected cells and discovered non-structural pro- teins forming tubules in the cell as well as an RNA-binding protein. His group, which included co-workers A.A. (Albie) van Dijk, C.W. (Christine) Bremer, N.T. (Nico) van der Walt and M. (Michelle) Cloete, also studied the viral transcriptase, an enzyme essential for its replication, and the proteins found in the viral and sub-viral particles. Of crucial importance for future work was of the group-specific and serotype-specific
Broekman had previously done some differential staining on BTV-infected cells and obtained results which suggested that the virus contained DNA, but chemical ana- lysis of the isolated nucleic acid indicated that it was RNA. However, it was resistant to degradation by the enzyme RNase, again suggesting that it consisted of DNA.
106 Finally the melting behaviour and analytical ultracentrifugation confirmed that the physical characteristics of the nucleic acid were those of a double-stranded structure, although chemically it was clearly RNA. The conclusion that the virus had a double- stranded RNA (dsRNA) genome was revo- lutionary and not easily accepted at first. Fortunately it soon became known that si- milar results had recently been obtained in the USA with a human reovirus. Eventually it was found that African horsesickness virus and a number of other insect-borne viruses were dsRNA containing viruses and they were assigned to a genus known as orbiviruses within the family Reoviridae.
“Under the leadership of Huismans the research on BTV and AHSV remained at the forefront in international terms.”
There were further unique characteris-
tics of BTV to be discovered. The dsRNA
genome was shown to consist of ten sepa-
rate fragments of different sizes, each of which acts as a gene coding for a specific protein which either forms part of the virus or is produced in the infected cell. Furthermore, the viral RNA is encapsulated in a double protein coat or capsid. Many years
the identification
antigens of BTV and the demonstration that immunization with a purified outer capsid protein of the virus could protect sheep against infection. This discovery attracted worldwide attention
PART 3
History of Individual Disciplines
1908-2008
Years