By the mid 1970s the responsibility and financial burden of maintaining the rapidly expanding laboratories of the PRF was becoming too much of a burden for the board of trustees and approaches were made to the Department of Health to purchase the laboratories and take over their governance. The timing of the negotiations, which led to the official establishment of the NIV, was good for both sides. For the board it was monetary as they were unable to continue funding the research labs, especially as medical virology, with its attendant burgeoning costs, was a rapidly expanding field.

From the government's side a major public health concern was causing some alarm. This was the looming threat of viral haemorrhagic fevers and the related newly recognised formidable infectious diseases that were appearing on the African continent. The risk of importing exotic viral infections into the country, particularly from elsewhere in Africa, preoccupied government minds, especially as large numbers of migrant workers from Southern, south-eastern and Central Africa were employed in South African mines. It was clear that there was an urgent need to establish an institute of public health excellence in viral infections.

An agreement was reached, which saw the Department of Health purchasing the viral research component of the PRF, its site and the buildings – which would become the future NICD – for the sum of R1.3 million. The NIV duly came into being on 1 April 1976. Whoever chose that date was probably oblivious to the humorous side of that choice. While the move was necessary and timely, the shift into a government office was a serious mistake. The petty civil service rules and restrictions that came with the move greatly encumbered the functioning of the new institute. To make matters worse, South Africa had become a pariah state in the apartheid years and the accompanying international ostracism further handicapped the development of the NIV as a scientific institution.

From the Department of Health's perspective, their concerns had not been unfounded. These were quite dramatically brought to a head in early 1975 when the first recognised viral haemorrhagic fever case in South Africa was recorded.