Antibodies are key components of the immune system, as they recognize and bind to proteins on the surfaces of viruses and bacteria. It was generally thought that any antibody-virus combinations that resulted were cleared by specialized immune cells, but a paper released yesterday by PNAS indicates that when any cell is targeted by a virus that has an antibody latched on to it, the cell can use the antibody to target the virus for destruction. It appears to be an important finding, but it's nowhere close to being a cure for the common cold, as some outlets have suggested.
First, the findings. The scientists were looking at a family of proteins called the TRIMs, many of which have antiviral activity. For the most part, the antiviral proteins act by binding directly to the virus once it gets inside the cell and targeting it for destruction. But, in one case, TRIM21, the protein didn't seem to bind to any viruses; instead, it had a high affinity for antibodies. This was pretty confusing; TRIM21 normally lives inside a cell, but antibodies are on the outside.
The authors came up with a hypothesis to explain this discrepancy: what if the antibodies were carried inside the cell with the virus? To test this idea, they incubated a virus (adenovirus) with antibodies that recognized it, and then placed the mixture in with some cells. A half an hour later, both the antibodies and the virus were inside the cells. Better still, TRIM21 was associated with them. So, it appears that TRIM21 functions to recognize antibody-tagged viruses inside the cell.
But what does it do with them? The first thing the authors checked was whether it had any influence on viral infection by creating cell lines with and without TRIM21, and infecting each with antibody-tagged virus. Infection rates dropped 60-fold when TRIM21 was around, and returned to nearly normal when TRIM21 was absent. So, it appears that the combination of an antibody and TRIM21 was killing the virus.
Based on the TRIM21 protein structure, the authors concluded that it was likely to be targeting the virus-antibody for destruction. TRIM21 has a section that normally attaches a small protein called ubiquitin to other proteins; ubiquitin signals a complex called the proteasome to digest them. So, the researchers confirmed that ubiquitin was also present in the virus-antibody-TRIM21 complex, and showed that blocking the proteasome was helped restore the virus' infectivity.
It appears that TRIM21 doesn't actually tag the virus with ubiquitin; instead, it tags itself, attracting the proteasome to the complex, where it chops everything—the virus, the antibody, probably TRIM21 itself—into harmless pieces.
The authors speculate that we've actually been seeing this behavior for years in a variety of experiments—it's just that, in the absence of an explanation, we've written it off as an anomaly or experimental error. The end of the paper's discussion contains a long list of work that should probably be reevaluated in light of the new findings.
These are potentially significant results, although it would be good to have a better sense of how widespread and significant this phenomenon is. Still, one thing it's clearly not is the end of viral disease, even assuming we could somehow boost this system. For starters, the whole thing relies on antibodies that recognize a specific virus, which we wouldn't have unless we'd already been exposed to or vaccinated against the virus. As both the cold and flu viruses demonstrate, viruses evolve fast enough that they're always moving targets.
In addition, this only works when an entire virus, antibodies and all, is carried into the cell. Many viruses, including some cold viruses and HIV, have a coat that ends up left at the membrane, along with any antibodies stuck to it. Only a protected inner shell makes its way inside the cell, with no antibodies for TRIM21 to recognize.
So, we're still largely stuck where we were previously, with vaccines still being the best way to produce antibodies, and some viruses steadfastly resisting our attempts to develop vaccines. Control over this new system might ultimately help us lessen the impact of an infection once it's gone on long enough to induce antibodies, but that's a long way from eliminating the common cold.