virology blog
About viruses and viral disease
The TWiVsters explain how superspreader bacteriophages release intact DNA from infected cells, and the role of astrocytes in protecting the cerebellum from virus infection.
You can find TWiV #428 at microbe.tv/twiv, or listen below.
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Back in 1974, before it was possible to determine the sequence of a viral genome, before we knew much about the origin of viruses and their ability to move genes from organism to organism, Lewis Thomas wrote the following incredibly prescient words in The Lives of a Cell:
The viruses, instead of being single-minded agents of disease and death, now begin to look more like mobile genes. We live in a dancing matrix of viruses; they dart, rather like bees, from organism to organism, from plant to insect to mammal to me and back again, and into the sea, tugging along pieces of this genome, strings of genes from that, transplanting grafts of DNA, passing around heredity as though at a great party. They may be a mechanism for keeping new, mutant kinds of DNA in the widest circulation among us. If this is true, the odd virus disease, on which we must focus so much of our attention in medicine, may be looked on as an accident, something dropped.
When Thomas wrote these words we knew that bacteriophages could move pieces of DNA from bacterium to bacterium, but we had no idea of the global scale of this movement. We did not know that most viruses could carry genes from cell to cell, nor did we appreciate that viruses could be beneficial. I am amazed by the accuracy of his words written at a time when we knew so little.
Norton Zinder made two important discoveries in the field of virology. While a Ph.D. student with Joshua Lederberg at the University of Wisconsin-Madison he found that viruses of bacteria (bacteriophages) could move genes from one host to another, a process called transduction. Later in his own laboratory at The Rockefeller University he isolated the first bacteriophages that contain RNA as genetic material. These were seminal findings in the growing field of molecular biology.
By the 1950s it was well known that different strains of the bacterium Escherichia coli could exchange genes in a process called recombination. Zinder wanted to know if other bacteria could also exchange genes in a similar manner, and therefore began to study Salmonella typhimurium. The strains that Zinder used for his experiments were lysogens: their chromosomal DNA contained integrated copies of the DNA genomes of bacteriophages. Zinder readily detected genetic exchange in Salmonella, but suspected that the latent phages might play a role. To test this idea, he grew Salmonella in tubes that were connected by a fine filter that allowed passage of viruses but not bacteria between the two cultures. The results showed that a filterable agent, or virus, could mediate the exchange of genetic material between bacterial strains; direct contact between bacteria was not necessary. The authors coined transduction to describe this process. We now understand that transduction occurs because bacteriophages may incorporate bacterial DNA into the viral particle. Transduction remains a common tool to stably introduce a foreign gene into a host cell.
Zinder describes the discovery of RNA-containing bacteriophages, which took place after he had moved to The Rockefeller University, in the Preface to RNA Phages:
In the late fifties, Tim Loeb, a new graduate student at The Rockefeller University, came into my laboratory and asked whether I thought it was possible that there were male-specific bacteriophages for E. coli. I….quickly responded in the affirmative and off he went to a raw sewage plant in New York City. …f2, the second isolate, was chosen for further study. Little did we think at the time that a whole new area of study was in the offing….
The first two bacteriophages that Loeb had isolated from New York City sewage were called f1 and f2. During purification of the phages it was clear that the genome of f1 was DNA. Chemical analyses subsequently demonstrated that the genome of f2 was RNA (later found to be positive-strand RNA). Similar phages were since isolated all over the world, and their study provided much basic information on viral replication, protein biosynthesis, and genome replication. The first genome sequence determined was in 1976 for the related RNA bacteriophage MS2.
Update: Moving eulogy by Jeffrey Ravetch in Eulogy for a brilliant mentor and teacher.
Loeb, T. (1961). A Bacteriophage Containing RNA Proceedings of the National Academy of Sciences, 47 (3), 282-289 DOI: 10.1073/pnas.47.3.282