Principles of Virology, Volume 1. Jane Flint

Principles of Virology, Volume 1 - Jane Flint


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      The student is invited to conjure up other plausible explanations.

       Damaso CR. 2018. Revisiting Jenner’s mysteries, the role of the Beaugency lymph in the evolutionary path of ancient smallpox vaccines. Lancet Infect Dis 18:e55–e63.

       Esparza J, Schrick L, Damaso CR, Nitsche A. 2017. Equination (inoculation of horsepox): an early alternative to vaccination (inoculation of cowpox) and the potential role of horsepox virus in the origin of the smallpox vaccine. Vaccine 35:7222–7230.

       Schrick L, Tausch SH, Dabrowski PW, Damaso CR, Esparza J, Nitsche A. 2017. An early American smallpox vaccine based on horsepox. N Engl J Med 377:1491–1492.

       TWIV 478: A pox on your horse. http://www.microbe.tv/twiv/twiv-478/.

       The organism must be regularly associated with the disease and its characteristic lesions.

       The organism must be isolated from the diseased host and grown in culture.

       The disease must be reproduced when a pure culture of the organism is introduced into a healthy, susceptible host.

       The same organism must be reisolated from the experimentally infected host.

      Not only were the tobacco mosaic and foot-and-mouth disease pathogens much smaller than any previously recognized microorganism, but also they could only reproduce in their host organisms. For example, extracts of an infected tobacco plant diluted into sterile solution produced no additional infectious agents until introduced into leaves of healthy plants, which subsequently developed tobacco mosaic disease. The serial transmission of infection by diluted extracts established that these diseases were not caused by a bacterial toxin present in the original preparations derived from infected tobacco plants or cattle. The failure of both pathogens to multiply in solutions that readily supported the growth of bacteria, as well as their dependence on host organisms for reproduction, further distinguished these new agents from pathogenic bacteria. Beijerinck termed the submicroscopic agent responsible for tobacco mosaic disease contagium vivum fluidum to emphasize its infectious nature and distinctive reproductive and physical properties. Agents passing through filters that retain bacteria came to be called ultrafilterable viruses, appropriating the term virus from the Latin for “poison.” This term was simplified eventually to “virus.”

      DISCUSSION

       New methods amend Koch’s principles

      While it is clear that a microbe that fulfills Koch’s postulates is almost certainly the cause of the disease in question, we now know that microbes that do not fulfill such criteria may still represent the etiological agents of disease. In the latter part of the 20th century, new methods were developed to associate particular viruses with disease based on immunological evidence of infection, for example, the presence of antibodies in blood. The availability of these methods led to the proposal of modified “molecular Koch’s postulates” based on the application of molecular techniques to monitor the role played by virulence genes in bacteria.

      The most revolutionary advances in our ability to link particular viruses with disease (or benefit) come from the more recent development of high-throughput nucleic acid sequencing methods and bioinformatics tools that allow detection of viral genetic material directly in environmental or biological samples, an approach called viral metagenomics. Based on these developments, alternative “metagenomic Koch’s postulates” have been proposed in which (i) the definitive traits are molecular markers such as genes or full genomes that can uniquely distinguish samples obtained from diseased subjects from those obtained from matched, healthy control subjects and (ii) inoculating a healthy individual with a sample from a diseased subject results in transmission of the disease as well as the molecular markers.

       Falkow S. 1988. Molecular Koch’s postulates applied to microbial pathogenicity. Rev Infect Dis 10(Suppl 2):S274–S276.

       Fredricks DN, Relman DA. 1996. Sequence-based identification of microbial pathogens: a reconsideration of Koch’s postulates. Clin Microbiol Rev 9:18–33.

       Mokili JL, Rohwer F, Dutilh BE. 2012. Metagenomics and future perspectives in virus discovery. Curr Opin Virol 2:63–77.

       Racaniello V. 22 January 2010. Koch’s postulates in the 21st century. Virology Blog. http://www.virology.ws/2010/01/22/kochs-postulates-in-the-21st-century/.


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