| > > For the more straightforward diseases it's even relatively straightforward to show that a particular virus causes that particular disease, with enough work. > I'd be really interested what this work would look like. A stringent example: 1) Replicate the virus in cell culture and ensure you're isolating the virus while doing so. - A: homogenize and passage a virus containing sample. - B: passage it through cell culture. - C: dilute the supernatant from cell culture until the dilution, on average, has less than one virus per aliquot. - D: Use these aliquots to inoculate further cell culture. 2) Analyze all cultures - A: As, on average, some of the aliquots contained no virus, there should be a number of cultures which look identical to the uninfected controls. - B: Any cultures which show morphology or pathology distinct from the uninfected controls should contain specific virus particles and show specific viral RNA/DNA on a PCR test. Likewise, any cultures which look like the uninfected controls should be free of virus based on these tests. - C: If any cultures show morphology or pathology distinct from the uninfected controls but do not contain virus particles (given sufficient time for the virus to propagate and emerge from the cells), then you've got a thinker on your hands. Triage for contaminants or another disease causing agent. 3) After demonstrating that virus is the causal agent of the infected culture morphology or pathology, use multiple of these infected cultures to infect animals (and have control "infections" from the uninfected cultures). Then repeat this process from the infected animals to demonstrate that it is indeed the identified virus which causes the disease. If you can't use an animal model for the disease then you're stuck doing this in cell culture and comparing the infected culture cell morphology and pathology to that of cells in biopsies of diseased people. Pretty darn good evidence that it is a virus, and a particular virus at that, which causes the disease. Realistically it's much more convenient just to use 2B as evidence. You get some issues with natural immunity and lysogenic versus lytic viral stages (these have different terms in Eukaryotic viral infection), but it's pretty decent for showing things like HIV being the causative factor of AIDS even prior to showing the effect of HIV presence in immune cells. |