Amending Koch's postulates for viral disease: When "growth in pure culture" leads to a loss of virulence.
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.
Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 South 4th Street, Hamilton, MT 59840, USA. Electronic address: prescottjb@niaid.nih.gov.
Joseph
J
Prescott
Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 South 4th Street, Hamilton, MT 59840, USA; Department of Medical Microbiology, University of Manitoba, 745 Bannatyne Avenue, Winnipeg, MB R3E 0J9, Canada.
Heinz
H
Feldmann
Zoonotic Diseases and Special Pathogens, National Microbiology Laboratory, Public Health Agency of Canada, 1015 Arlington Street, Winnipeg, MB R3E 3R2, Canada; Department of Medical Microbiology, University of Manitoba, 745 Bannatyne Avenue, Winnipeg, MB R3E 0J9, Canada. Electronic address: david.safronetz@phac-aspc.gc.ca.
David
D
Safronetz
D000220:Adaptation, Biological; D000818:Animals; D002044:Bunyaviridae Infections / Q000821:virology; D003470:Culture Media; D046508:Culture Techniques; D004195:Disease Models, Animal; D006476:Orthohantavirus / Q000235:genetics / Q000254:growth & development / Q000472:pathogenicity; D006801:Humans; D051379:Mice; D011323:Primates; D014774:Virulence; D014776:Virus Cultivation; D014780:Viruses / Q000235:genetics / Q000254:growth & development* / Q000472:pathogenicity*
D003470:Culture Media
Adaptation; Attenuation; Cell culture; Disease modeling; Viral pathogens; Virus