viruses

the-wasps-that-tamed-viruses

The wasps that tamed viruses

Parasitoid wasp

Enlarge / Xorides praecatorius is a parasitoid wasp.

If you puncture the ovary of a wasp called Microplitis demolitor, viruses squirt out in vast quantities, shimmering like iridescent blue toothpaste. “It’s very beautiful, and just amazing that there’s so much virus made in there,” says Gaelen Burke, an entomologist at the University of Georgia.

M. demolitor  is a parasite that lays its eggs in caterpillars, and the particles in its ovaries are “domesticated” viruses that have been tuned to persist harmlessly in wasps and serve their purposes. The virus particles are injected into the caterpillar through the wasp’s stinger, along with the wasp’s own eggs. The viruses then dump their contents into the caterpillar’s cells, delivering genes that are unlike those in a normal virus. Those genes suppress the caterpillar’s immune system and control its development, turning it into a harmless nursery for the wasp’s young.

The insect world is full of species of parasitic wasps that spend their infancy eating other insects alive. And for reasons that scientists don’t fully understand, they have repeatedly adopted and tamed wild, disease-causing viruses and turned them into biological weapons. Half a dozen examples already are described, and new research hints at many more.

By studying viruses at different stages of domestication, researchers today are untangling how the process unfolds.

Partners in diversification

The quintessential example of a wasp-domesticated virus involves a group called the bracoviruses, which are thought to be descended from a virus that infected a wasp, or its caterpillar host, about 100 million years ago. That ancient virus spliced its DNA into the genome of the wasp. From then on, it was part of the wasp, passed on to each new generation.

Over time, the wasps diversified into new species, and their viruses diversified with them. Bracoviruses are now found in some 50,000 wasp species, including M. demolitor. Other domesticated viruses are descended from different wild viruses that entered wasp genomes at various times.

Researchers debate whether domesticated viruses should be called viruses at all. “Some people say that it’s definitely still a virus; others say it’s integrated, and so it’s a part of the wasp,” says Marcel Dicke, an ecologist at Wageningen University in the Netherlands who described how domesticated viruses indirectly affect plants and other organisms in a 2020 paper in the Annual Review of Entomology.

As the wasp-virus composite evolves, the virus genome becomes scattered through the wasp’s DNA. Some genes decay, but a core set is preserved—those essential for making the original virus’s infectious particles. “The parts are all in these different locations in the wasp genome. But they still can talk to each other. And they still make products that cooperate with each other to make virus particles,” says Michael Strand, an entomologist at the University of Georgia. But instead of containing a complete viral genome, as a wild virus would, domesticated virus particles serve as delivery vehicles for the wasp’s weapons.

Here are the steps in the life of a parasitic wasp that harbors a bracovirus.

Enlarge / Here are the steps in the life of a parasitic wasp that harbors a bracovirus.

Those weapons vary widely. Some are proteins, while others are genes on short segments of DNA. Most bear little resemblance to anything found in wasps or viruses, so it’s unclear where they originated. And they are constantly changing, locked in evolutionary arms races with the defenses of the caterpillars or other hosts.

In many cases, researchers have yet to discover even what the genes and proteins do inside the wasps’ hosts or prove that they function as weapons. But they have untangled some details.

For example, M. demolitor  wasps use bracoviruses to deliver a gene called glc1.8  into the immune cells of moth caterpillars. The glc1.8  gene causes the infected immune cells to produce mucus that prevents them from sticking to the wasp’s eggs. Other genes in M. demolitor’s bracoviruses force immune cells to kill themselves, while still others prevent caterpillars from smothering parasites in sheaths of melanin.

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We still don’t understand how one human apparently got bird flu from a cow

Holstein dairy cows in a freestall barn.

Enlarge / Holstein dairy cows in a freestall barn.

The US Department of Agriculture this week posted an unpublished version of its genetic analysis into the spillover and spread of bird flu into US dairy cattle, offering the most complete look yet at the data state and federal investigators have amassed in the unexpected and worrisome outbreak—and what it might mean.

The preprint analysis provides several significant insights into the outbreak—from when it may have actually started, just how much transmission we’re missing, stunning unknowns about the only human infection linked to the outbreak, and how much the virus continues to evolve in cows. The information is critical as flu experts fear the outbreak is heightening the ever-present risk that this wily flu virus will evolve to spread among humans and spark a pandemic.

But, the information hasn’t been easy to come by. Since March 25—when the USDA confirmed for the first time that a herd of US dairy cows had contracted the highly pathogenic avian influenza H5N1 virus—the agency has garnered international criticism for not sharing data quickly or completely. On April 21, the agency dumped over 200 genetic sequences into public databases amid pressure from outside experts. However, many of those sequences lack descriptive metadata, which normally contains basic and key bits of information, like when and where the viral sample was taken. Outside experts don’t have that crucial information, making independent analyses frustratingly limited. Thus, the new USDA analysis—which presumably includes that data—offers the best yet glimpse of the complete information on the outbreak.

Undetected spread

One of the big takeaways is that USDA researchers think the spillover of bird flu from wild birds to cattle began late last year, likely in December. Thus, the virus likely circulated undetected in dairy cows for around four months before the USDA’s March 25 confirmation of an infection in a Texas herd.

This timeline conclusion largely aligns with what outside experts previously gleaned from the limited publicly available data. So, it may not surprise those following the outbreak, but it is worrisome. Months of undetected spread raise significant concerns about the country’s ability to identify and swiftly respond to emerging infectious disease outbreaks—and whether public health responses have moved past the missteps seen in the early stages of the COVID-19 pandemic.

But another big finding from the preprint is how many gaps still exist in our current understanding of the outbreak. To date, the USDA has identified 36 herds in nine states that have been infected with H5N1. The good news from the genetic analysis is that the USDA can draw lines connecting most of them. USDA researchers reported that “direct movement of cattle based upon production practices” seems to explain how H5N1 hopped from the Texas panhandle region—where the initial spillover is thought to have occurred—to nine other states, some as far-flung as North Carolina, Michigan, and Idaho.

Bayes factors for inferred movement between different discrete traits of H5N1 clade 2.3.4.4b viruses demonstrating the frequency of movement.

Enlarge / Bayes factors for inferred movement between different discrete traits of H5N1 clade 2.3.4.4b viruses demonstrating the frequency of movement.

Putative transmission pathways of HPAI H5N1 clade 2.3.4.4b genotype B3.13 supported by epidemiological links, animal movements, and genomic analysis.

Enlarge / Putative transmission pathways of HPAI H5N1 clade 2.3.4.4b genotype B3.13 supported by epidemiological links, animal movements, and genomic analysis.

Putative transmission pathways of HPAI H5N1 clade 2.3.4.4b genotype B3.13 supported by epidemiological links, animal movements, and genomic analysis. [/ars_img]The bad news is that those lines connecting the herds aren’t solid. There are gaps in which the genetic data suggests unidentified transmission occurred, maybe in unsampled cows, maybe in other animals entirely. The genetic data is clear that once this strain of bird flu—H5N1 clade 2.3.4.4 genotype B3.13 —hopped into cattle, it could readily spread to other mammals. The genetic data links viruses from cattle moving many times into other animals: There were five cattle-to-poultry jumps, one cattle-to-raccoon transmission, two events where the virus moved from cattle to domestic cats, and three times when the virus from cattle spilled back into wild birds.

“We cannot exclude the possibility that this genotype is circulating in unsampled locations and hosts as the existing analysis suggests that data are missing and undersurveillance may obscure transmission inferred using phylogenetic methods,” the USDA researchers wrote in their preprint.

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