Most contemporary virologists use the term replication to indicate either the production of new virus particles or viral genomes. Because these are very different processes, during the preparation of the fourth edition of the textbook Principles of Virology, the authors decided to use the word reproduction to designate the production of new infectious virus particles, and replication when referring to nucleic acid synthesis. Recently I learned from Bill Summers, speaking at ASV 2019, how the historical use of these two words reflects our evolving concept of virus.
While we have understood for 150 years that viruses cause disease, their physical and biological properties were not always clear. An early definition was that the infectivity of agents causing diseases of plants was â€˜filtrableâ€™, leading Beijerinck in 1898 to call them â€˜contagious living fluidsâ€™. When bacteriophages were first visualized by the electron microscope in 1939, it was obvious that viruses were particulate. The crystallization of tobacco mosaic virus in 1935 lead many to think that viruses were not organisms but chemicals. Stanley, who carried out this work, thought that viruses were infectious proteins!
If viruses were chemicals, then how did they multiply? As Summers writes:
It is interesting to note that the discussion during this period was almost invariably framed in terms of â€œreproduction,â€ firmly locating the problem in the realm of biology, not â€œreplication,â€ a later term favored by the chemists and now part of the modern discourse in virology.
At this time the word â€˜replicationâ€™ had not entered into lexicon of virologists. Not until 1952, when Hershey and Chase showed that DNA is the genetic material of viruses, did â€˜replicationâ€™ begin to be used by those studying viruses. In Luriaâ€™s 1953 textbook General Virology, the term reproduction can be found many times, but replication only appears twice. The following sentence beautifully illustrates the distinct usage of the two words in 1953 (emphasis mine):
The results suggest a special mode of phage reproduction, in which the chromosomes are replicated by a linear, zipper-like mechanism.
As Summers points out, today nearly every virologist uses the word replication to mean either the synthesis of new virus particles or new genomes. We did the same for the first two editions of Principles of Virology. Iâ€™m not sure when replication became ensconced in the virology lexicon, but I feel that having separate terms for production of nucleic acids and virus particles is more precise, removing ambiguity about what is being discussed.
When we first wrote Principles of Virology, we emulated Luriaâ€™s General Virology in presenting principles and patterns, not patchworks. Little did we know that we would also return to Luriaâ€™s use of reproduction and replication to describe distinct processes.