A negative viral culture result is not the end of the story...just a negative result

Lately, for both Ebola virus and Middle East respiratory syndrome coronavirus, there have been instances where I've been reminded that one must not rely on the growth of an infectious virus from a sample to be sure that there is virus in that sample.

Past diagnostic methods have failed to isolate many newly identified viruses (NIVs), which is not surprising considering that those culture-based methods can be over 100-fold less sensitive than current molecular (PCR-based) tests [1,2,3,4] and that many new viruses do not grow in traditional culture at all.

So when an RT-PCR or PCR result cannot be confirmed by the culture of a virus from the same sample, that really doesn't mean more than...that. 

Virus may be present, but our relatively insensitive culture techniques, which haven't really advanced in a long time, may just fail to get it growing. 

Viral isolation by cell culture is really a dying art form. And it is a very lengthy, demanding and sometimes subjective art form at that requiring particularly skilled artistes. 

References...

1. Templeton,K.E. et al. Improved diagnosis of the etiology of community-acquired pneumonia with real-time polymerase chain reaction. Clin Infect Dis 41, 345-351 (2005).
2. van Kraaij,M.G.J. et al. Frequent detection of respiratory viruses in adult recipients of stem cell transplants with the use of real-time polymerase chain reaction, compared with viral culture. Clin Infect Dis 40, (2005).
3. Garbino,J. et al. Lower respiratory viral illnesses: Improved diagnosis by molecular methods and clinical impact. Am J Resp Crit Care Med 170, (2004).
4. Gunson,R.N., Collins,T.C., & Carman,W.F. Real-time RT-PCR detection of 12 respiratory viral infections in four triplex reactions. Journal of Clinical Virology(2005).