Table 2.

Examples of the alteration of viral virulence upon propagation in cell culture.

Virus	Outcome of cell culture passage
Sin Nombre hantavirus	Vero-passaged virus is completely attenuated in NHPs, whereas virus propagated in deer mice causes severe disease (Safronetz et al., 2013).
Puumala hantavirus	Virus passaged in the reservoir (bank vole) causes disease in NHPs, but virus passaged in Vero cells does not (Klingstrom et al., 2002).
Ebola virus	Accumulation of adenosine residues in the GP gene editing site upon passage in Vero cells leads to attenuation in guinea pigs (Volchkova et al., 2011).
Measles virus	Cell culture adapted viruses lose pathogenicity in vivo due to a loss in interferon antagonism (Bankamp et al., 2008).
	Passage in Vero cells results in a change in entry receptor usage and a decrease in pathogenicity in vivo (Dörig et al., 1993).
Foot and mouth disease virus	Passage in culture results in a receptor switch between αvβ3 integrin and heparan sulfate (Martinez et al., 1997).
Sindbis virus	Virus grown on mosquito cells demonstrated increased infectiousness for human dendritic cells when compared to virus grown on Chinese hamster cells (Klimstra et al., 2003).
Rift Valley fever virus	Virus passaged on mosquito cells retains virulence, whereas when the virus is passaged on Vero cells, in vivo virulence is lost (Weingartl et al., 2014b).