Amending Koch's postulates for viral disease: When “growth in pure culture” leads to a loss of virulence

- Standard laboratory practice of amplifying viruses in cell culture can lead to genetic changes in the viral genome.
- In vitro adaption of viruses can alter the viral phenotype in vivo.
- Scientist should be aware of possible consequences these processes may have on research and the interpretation of results.

It is a common laboratory practice to propagate viruses in cell culture. While convenient, these methodologies often result in unintentional genetic alterations, which have led to adaptation and even attenuation in animal models of disease. An example is the attenuation of hantaviruses (family: Bunyaviridae, genus: Hantavirus) when cultured in vitro. In this case, viruses propagated in the natural reservoir species cause disease in nonhuman primates that closely mimics the human disease, but passaging in cell culture attenuates these viruses to the extent that do not cause any measurable disease in nonhuman primates. As efforts to develop animal models progress, it will be important to take into account the influences that culture in vitro may have on the virulence of viruses. In this review we discuss this phenomenon in the context of past and recent examples in the published literature.