When HIV jumped from chimpanzees to humans sometime in the early 1900s, it crossed a gulf spanning several million years of evolution. But tobacco ringspot virus, scientists announced last week, has made a jump that defies credulity. It has crossed a yawning chasm ~1.6 billion years wide.

And this is likely bad news for its new host, the honeybee, matchmaker of crops and bringer of honey. These are two services for which humans are both eternally indebted, and, in the case of the former, possibly unable to live without. Bees pollinate the majority of our fruit and nut crops and many vegetables -- some 90 all told -- without which humanity would be nutritionally impoverished. Yet shortages are a possibility we are confronting, as bee populations in America have declined in recent years for reasons that seem to be both diverse and elusive. Colony collapse disorder, as whatever it is is called, was first reported in 2006 and has spread globally. Many viruses, parasites, and pesticides have been implicated, but no smoking gun has emerged.

As scientists were studying the possible role of pollen in spreading known bee viruses, a team of scientists from the United States and China began screening bees and pollen for viruses of all sorts. To their surprise, as they reported Jan. 21 in the journal mBio, they discovered a common plant virus -- tobacco ringspot virus -- had seemingly infested honeybees. Was it merely a transient visitor? Or had it made itself at home in a place inconceivably different from its usual digs?

Their first clue was the virus's genome. Tobacco ringspot virus is an RNA virus. Though DNA acts as a stable repository of instructions for building proteins, RNA is how that information is transmitted to the part of the cell that manufactures them. It is transient by nature, and recycled after a short time. As a result, RNA polymerase, the enzyme that makes RNA by copying DNA, is not as careful as DNA polymerase, the enzyme that replicates it. It lacks a key proofreading mechanism that DNA polymerase has (3'->5' proofreading), and as a result, is more likely to make mistakes called mutations. In humans, that is not a problem, because the life of an individual strand of RNA is brief and any mistakes end with its destruction.

But for RNA viruses, their hereditary information is RNA, and the extremely high RNA virus mutation rate is a powerful engine of evolution. It generates the diversity on which natural selection can act. Mistakes can lead quickly to deformed or malfunctioning virions (no big deal for viruses) or to new host conquests (big deal for viruses) alike. RNA viruses have generated many celebrities; HIV is an RNA virus, as are SARS and influenza. RNA viruses are the most likely source of host-jumping viruses or an infection that suddenly acquires greater virulence, the authors of the study said.

Still, a leap between kingdoms is not an everyday event. Most plant viruses do rely on plant-eating insects to swap hosts. But very few of them actually infect those insects. One exception is the Rhabdoviridae, the family of viruses that includes rabies. Some viruses in that family have long been known to infect both plant and animal hosts.

In spite of its name, tobacco ringspot virus infects many plants besides tobacco from more than 35 families, including tomato, cucumber, beans, and many woody plants. This is a virus that loves plants, although they assuredly don't love it back. It can stunt or kill the plant, possibly discoloring the leaves in a characteristic ringspot pattern in the process.

Tobacco ringspot virus is spread between plants in any number of ways -- the virus is not picky. It can be transmitted directly to the next generation by infected seed. Or it can be passed from one plant to another by a dagger nematode, a tiny soil worm with a piercing stylus for sucking plant juices. Any number of other plant-sucking or leaf-eating insects can do the job, too: aphids, thrips, grasshoppers, or tobacco flea beetles, perhaps. Or honeybees. The bees can spread the virus to a new plant via infected pollen.

Which brings us back to the mysterious matter of the plant virus that appeared in a bee, how it might have gotten there, and what it might be doing. Bees handle pollen in some fairly intimate ways. Their bodies are electrically charged so that pollen sticks, but they also carry baskets on their hind legs into which they stuff gobs of the stuff. Then, back at the hive, they mix the pollen into "bee bread", by combining it with honey and their own glandular secretions, which they may later eat. In short, bees wallow in pollen like hogs in slop, ensuring that any enterprising pollen-borne viruses have both means and motive to make a host leap. Whether the virus had established long-term residency in its new host was unknown, though.

The scientists sampled tissue from throughout the bees' bodies to see if was concentrated in their gut and salivary glands, where it would be most expected if it was just passing through. They found something very different. The virus did not appear to replicate at all in their guts or salivary glands, and very few virus particles were found there. Instead, the virus had spread throughout bees' bodies and replicated particularly well in their wings, nerves, antennae, trachea, and blood (technically, hemolymph). Ominously, it seemed to especially favor nervous tissue. Far from being a polite and unintrusive guest, it looked like the virus had picked the front door lock, raided the fridge and keg, and called to start the cable TV.

But the news for bees got worse. When the scientists looked inside the mites Varroa destructor, which have been implicated in colony collapse disorder and make a living as a nasty tick-like parasite of bees (if ticks were the size of dinner plates), their guts were full of tobacco ringspot virus. As with ticks, Varroa mites sap their hosts' energy and are known to spread disease. But unlike the bees, the mites' tobacco ringspot infections were limited to their gut, vastly decreasing the possibility of a silver lining in which the virus preyed on bee parasites as well as bees.

To see what the viruses themselves might reveal about what had happened, the scientists compared tobacco ringspot genes from plants, bees, and mites. The viruses in bees and mites were closely related, implying the mites picked up the virus from the bees, and that they both came by their virus via a common ancestor -- a single ill-starred encounter between a particular bee and a particular grain of pollen, perhaps. Moreover, bee pollen stashed in the hive -- that "bee bread" stuff mentioned earlier -- was contaminated with the same strain.

But the presence of virus alone throughout bee bodies doesn't reveal whether the virus is causing harm. So the scientists sampled six strong and four weak hives of bees over the course of a year in order to see whether tobacco ringspot might be having any deleterious effects on its new mobile home. They looked for that virus and a variety of other viruses implicated in colony collapse disorder -- among them, Deformed Wing Bee Virus (DWV), Black Queen Cell Virus (BQCV), and Israel Acute Paralysis Virus (IAPV). Indeed, higher concentrations of tobacco ringspot and these other viruses seemed to presage colony collapse.

Many other unknowns remain. The team doesn't know if the virus can persist in bees without frequent re-introduction from pollen. They also don't know if the bees can give the virus back to uninfected plants. And of course, whether these suspicious viruses are jointly the cause of collapse, a symptom of some other underlying malady (weakened bees may be more prone to viral infection), or both, remains difficult to say. The story of colony collapse disorder remains unfinished.

It's worth reflecting on why this particular viral invasion is so remarkable. A virus wishing to conquer any new host -- much less one separated from the established host by more than a billion years of evolution -- must overcome several substantial obstacles. It must encounter the new host. Its coat proteins must evolve such that they permit it to gain entry to hosts' cells, although a change to one or a few protein subunits called amino acids may be enough to get the job done. Then, the virus's genome must evolve to let it evade its new host's immune system and hijack its cellular replication machinery. Finally, the virus must find a way to spread from one new host to another. It's a tall order, and that tobacco ringspot appears to have accomplished it all seems extraordinary.

According to the authors of this study, this is the first evidence that honeybees can be infected by plant-virus contaminated pollen, but it might not have been the first or last. About 5% of plant viruses are pollen-borne. The genetic material of most? RNA.

Reference

Li J.L., Cornman R.S., Evans J.D., Pettis J.S., Zhao Y., Murphy C., Peng W.J., Wu J., Hamilton M. & Boncristiani H.F. & (2013). Systemic Spread and Propagation of a Plant-Pathogenic Virus in European Honeybees, Apis mellifera, mBio, 5 (1) e00898-13-e00898-13. DOI: 10.1128/mBio.00898-13