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Giant viruses may be attacking the microbes in our guts

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Enlarge / Phages on the surface of a bacterial cell.

In many cases, viruses manage to spread so readily because they’re so compact, allowing hundreds of thousands of viral particles to explode from a single sneeze. That compact size comes in part from their limited needs. Since viruses use parts of their host cells for much of what they need to do, even the more complicated viruses tend to only need a few dozen specialized genes to do things like evade the immune system or remain dormant in cells. In fact, complexity would seem to go against one of virus’ evolutionary advantages: the ability to make lots of copies of itself very quickly.

So it was a bit of a surprise to find that there are giant viruses that carry far more genetic material than they seemingly need. All cells carry the machinery needed to make proteins so, at most, viruses typically carry just a few genes that direct the machinery to focus on the virus’ needs. But the giant viruses seemed to carry replacements for much of the basic machinery itself. Those viruses were attacking complicated cells, with a lot of internal structures and many complex biological processes going on in different locations. Maybe carrying all those seemingly superfluous parts was advantageous in that context.

Or possibly not. In a study released today, researchers describe a large collection of giant viruses that target bacteria. While smaller than some of the largest eukaryotic viruses, they’re not that much smaller. And given that they infect bacteria, the genomes of the newly described viruses may be a substantial fraction of the size of their host’s genome.

In the mix

The work relies on what has come to be called meta-genomics, which essentially involves blowing up all the cells in an environmental sample and sequencing any DNA that comes out. This will provide DNA sequence data on all of the different microbes living in it, as well as the viruses living in them. Software can search through that data and find pieces that overlap, stitching together larger sections of the genome from the smaller fragments of sequence. But it’s difficult to put together an entire genome this way, as any repeated sequences or difficult-to-sequence segments will confuse the computer. So even if giant viruses are in these samples, a metagenomic analysis would typically identify smaller fragments of them and not link them together to reveal their full size.

Inspired by some earlier indications that bacteria-attacking viruses (technically termed “phages”) can get very large, an equally large research team got ahold of a lot of environmental samples and went searching for giant viruses. Sources included “human fecal and oral samples, fecal samples from other animals, freshwater lakes and rivers, marine ecosystems, sediments, hot springs, soils, deep subsurface habitats, and the built environment.”

Once software had assembled the short sequences of the original survey into longer fragments, the researchers checked for gene similarities to identify whether the fragment came from bacteria, complex cells, archaea, or viruses. Any sequences that were 200,000 bases long or more were tested to see if they might actually be circular (a common feature of large viral genomes in bacteria), and a handful of the largest ones were selected for detailed manual examination. “Manual” here meaning that grad students would have to confirm the sequencing and look for ways to deal with any repeated DNA or difficult sequences.

As a whole, the researchers put together 350 sequences of viruses, based on the fact that they carry genes involved in building the viruses’ coat or exploding their host cells in order to spread further. Four other long sequences were difficult to assign to any category.

Families of giants

Some of the apparent viruses were absolutely huge, with four being over 600,000 bases long, and the largest coming in at 735,000. This is in the same range as some of the large viruses that attack amoeba. But whereas the amoeba can have genomes that are hundreds of billions of bases long, these viruses seem to be infecting bacteria with genomes less than 5 million bases long. For context, there are bacteria with genomes that are only about one-fifth the size of these viruses.

One of the viruses had a gene that was over 2,300 bases long—1.5 times the size of the entire genome of some small viruses.

With the assembly complete, the researchers started comparing sequences to figure out what these viruses were related to. In many cases, the answer turned out to be “each other.” The largest viruses were all part of a family that the researchers termed “Mahaphages” (Maha being the Sanskrit word for huge). Significantly, there were no small viruses that grouped among the giants, indicating that these huge genomes are probably stable features of this family rather than being the result of a smaller virus that happened to gain a lot of extra DNA recently.

Many of these viral families have genes for the transfer RNAs used in making proteins, which are normally supplied by the cell. Other genes include those needed for the metabolism of nucleic acids, allowing them to make some of the DNA and RNA they’re dependent on. Normally, both of these classes of genes are provided by the host, although similar things are found in the giant viruses that infect amoeba. The authors note that this sort of gene content is similar to a group of tiny bacteria with small genomes that are thought to be symbiotic or parasitic. Whether this is simply a consequence of lifestyle or represents something more significant is left to future studies.

CRISPR-y

Many of the viruses also carry components of the CRISPR/Cas system that we’ve started using for genome editing. Bacteria typically use this system to protect themselves from viruses, which makes it odd to find viruses carrying their own version. Some of these systems seem to target genes that bacteria use to control gene activity, so the virus’ version may simply involve redirecting these control systems to focus on virus production. In other cases, they target different viruses, suggesting that they’re a way of limiting competitors.

Other families of viruses seem to carry proteins that shut the bacterial CRISPR system down, which is more in line with what you’d expect—a means of protecting the virus from the host’s defenses.

Perhaps the strangest thing found in these viruses are genes that encode relatives of a protein called tubulin, which helps a cell organize its internal contents. Bacteria are rather notable for having a poorly defined internal organization, so seeing a virus leveraging something we don’t understand especially well is rather striking. Still, it’s easy to see how this protein could help get all the pieces needed for assembling a virus to the right place.

But there’s clearly a lot we don’t understand about these viruses more generally, including the specific cells they infect—we know the environment they came from and the genuses of bacteria they’re generally found with, but not a whole lot more than that. Figuring out more and studying their dynamics in culture may help us understand how the viruses can sometimes outcompete their smaller and faster-moving relatives.In the process, they might teach us some lessons about the bacteria they’re infecting.

Nature, 2020. DOI: 10.1038/s41586-020-2007-4 (About DOIs).

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As Florida punishes schools, study finds masks cut school COVID outbreaks 3.5X

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Enlarge / A second-grade teacher talks to her class during the first day of school at Tustin Ranch Elementary School in Tustin, CA on Wednesday, August 11, 2021.

Schools with universal masking were 3.5 times less likely to have a COVID-19 outbreak and saw rates of child COVID-19 cases 50 percent lower in their counties compared with schools without mask requirements. That’s according to two new studies published Friday by the Centers for Disease Control and Prevention.

The new data lands as masks continue to be a political and social flash point in the US. And children—many of whom are still ineligible for vaccination—have headed back into classrooms.

In one of the newly published studies, health researchers in Arizona looked at schools with and without mask policies in Maricopa and Pima Counties. Together, the counties account for more than 75 percent of the state’s population. The researchers identified 210 schools that had universal masking requirements from the start of their school years. They compared those to 480 schools that had no mask requirements throughout the study period, which ran from July 15 to August 30.

The researchers tallied 129 school-associated COVID-19 outbreaks in all of those schools during the study period. About 87.5 percent of the outbreaks were in schools without mask requirements. The researchers then ran an analysis, adjusting for school sizes, COVID-19 case rates in each school’s zip code, socioeconomics measures, and other factors. The researchers found that the odds of a school-associated COVID-19 outbreak were 3.5 times higher in the schools without mask requirements compared to those with universal masking.

In a separate study, CDC researchers tried to assess if schools’ mask policies have broader impacts for their communities—and they do. The researchers looked at county-level data on the rates of pediatric COVID-19 cases in 520 counties around the US. They compared rates of child COVID-19 cases in the week before and week after schools started their terms.

Though all counties generally saw increases in pediatric COVID-19 cases after schools started up, the counties with universally masked schools saw smaller bumps. For counties with school mask requirements, the average increase in case rates after schools started was 16.32 cases per 100,000 children per day. Counties without school mask requirements saw an average rate increase about twice as high—34.85 cases per 100,000 children per day.

Mask safety

The US continues to see a patchwork of mask use and other protective measures in schools as the 2021-2022 school year gets underway. Many schools in many states do not have universal masking requirements even though the CDC and the American Academy of Pediatrics both recommend universal masking in schools. In some states state leaders have prohibited schools from issuing mask requirements—and even penalized them for requiring masks.

Florida Governor Ron DeSantis is among the leaders who have banned mask mandates in schools. And, although the ban is being challenged in court, DeSantis is withholding money from school boards that have issued mask mandates anyway.

On Thursday, the US Department of Education announced that it had granted the school board of Florida’s Alachua County $147,719. The money is intended to “restore funding withheld by state leaders—such as salaries for school board members or superintendents who have had their pay cut—when a school district implemented strategies to help prevent the spread of COVID-19 in schools.”

In a statement, Alachua County Public School Superintendent Dr. Carlee Simon: “I’m very grateful to [US Secretary of Education Miguel] Cardona, President Biden and the federal government for the funding. But I’m even more grateful for their continued support and encouragement of our efforts to protect students and staff and to keep our schools open for in-person learning.”

Alachua is the first county in the nation to receive such funding, provided through the new Project to Support America’s Families and Educators (Project SAFE) grant program.

In a separate statement, education secretary Cardona said: “We should be thanking districts for using proven strategies that will keep schools open and safe, not punishing them. We stand with the dedicated educators in Alachua and across the country doing the right thing to protect their school communities.”

Public health experts say that masks are a critical tool to help protect children, teachers, and staff from the spread of the pandemic coronavirus, SARS-CoV-2. Masks are intended to be one key layer of a multi-layered approach that also includes vaccination for those eligible, physical distancing when possible, improved ventilation, testing, quarantining, improved hygiene, and disinfection and cleaning.

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NASA seeks a new ride for astronauts to the Artemis launch pad

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Enlarge / NASA first began using the 1983-model Airstream for space shuttle missions in 1984.

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NASA has asked industry for ideas to develop an “Artemis Crew Transportation Vehicle” that will take its astronauts from suit-up facilities to the launch pad on launch day.

The space agency, of course, has not launched its own astronauts on a NASA-built vehicle since the end of the space shuttle program in 2011. From 1984 through the end of the shuttle era, the agency used a modified Airstream motor home, known as the “Astrovan,” to ferry crews to the launch pad. This iconic vehicle had a shiny, silvery exterior but a fairly spartan interior. “The current vehicle’s appeal is rooted in its tradition rather than its décor,” the agency acknowledged in 2011.

Now, NASA is gearing up for a new era of deep space exploration, and it plans to launch four astronauts at a time inside the Orion spacecraft, on top of a Space Launch System rocket. The first human flights on these vehicles could occur in late 2023 or early 2024, NASA administrator Bill Nelson recently said.

While it has taken literally decades and tens of billions of dollars to develop the spacecraft and rocket, NASA is hoping its launch pad ride can be furnished a little more quickly. In its solicitation, released Friday, NASA says its “Artemis CTV” should be delivered no later than June 2023.

NASA is considering three different options for the new vehicle. A provider can custom-build a vehicle, modify a commercially available vehicle, or repair and refurbish the venerable Astrovan.

As part of its solicitation, NASA has a lengthy list of requirements for its Artemis transport vehicle. Among them:

  • It must be a zero-emission vehicle, such as battery-electric, plug-in hybrid electric, or fuel cell electric
  • It must have a carrying capacity of eight passengers, including four fully suited astronauts
  • It must have extensive capacity for equipment, including large bags for helmets, ice-based cooling units, and more
  • Have sufficiently wide doors of 24 to 36 inches for ingress and egress by suited astronauts

According to Ars automotive editor Jonathan Gitlin, it is unlikely that any existing zero-emissions vehicle meets these requirements, even with modifications. Ford’s forthcoming electric Transit Van may come close, Gitlin added.

NASA astronauts Doug Hurley, Chris Ferguson, and Sandy Magnus inside the Astrovan in 2011.
Enlarge / NASA astronauts Doug Hurley, Chris Ferguson, and Sandy Magnus inside the Astrovan in 2011.

NASA

The best option, in fact, may be renovating the old Airstream. This is because the vehicle will not be called upon for particularly long journeys—it’s only a few kilometers to and from the launch pad—and this demand would be well within the capabilities of a couple Tesla drive units and a slab of batteries.

With the Artemis program, NASA is going back to the Moon like it did in the 1960s. It’s using a capsule design, not dissimilar to Apollo, and a large rocket with space shuttle main engines designed in the 1970s. So, why shouldn’t astronaut transport be retro, too?

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CDC director overrules experts, allows Pfizer boosters for health workers

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Enlarge / CDC Director Rochelle Walensky testifies during a Senate committee hearing in July 2021.

Just past midnight last night, the director of the Centers for Disease Control and Prevention overruled a committee of independent advisers, allowing for use of a Pfizer/BioNTech vaccine booster dose in people with increased risk of occupational and institutional exposure to the pandemic coronavirus. That includes health care workers, front-line workers, teachers, day care providers, grocery store workers, and people who work or live in prisons and homeless shelters, among others.

Hours earlier, the CDC’s Advisory Committee on Immunization Practices (ACIP) concluded a two-day meeting on booster recommendations—and voted 9-6 against recommending boosters for this group.

“As CDC Director, it is my job to recognize where our actions can have the greatest impact,” Director Rochelle Walensky said in a statement. “At CDC, we are tasked with analyzing complex, often imperfect data to make concrete recommendations that optimize health. In a pandemic, even with uncertainty, we must take actions that we anticipate will do the greatest good.”

She further noted that the inclusion of people at high risk of COVID-19 from occupational and institutional exposure “aligns with the FDA’s booster authorization.” The Food and Drug Administration last Wednesday issued an amended Emergency Use Authorization for the Pfizer/BioNTech vaccine, which allowed booster doses for people 65 and older as well as people ages 18 to 64 who are at high risk of COVID-19 either from underlying medical conditions or occupational and institutional exposures.

Though the CDC’s advisory committee was torn over endorsing that use, they ultimately decided that the need was not there—vaccine effectiveness against severe disease and hospitalization remains very strong in those under age 65. And recommending boosters for anyone with a conceivable occupational or institutional risk could create a booster free-for-all.

By taking the unusual move to overrule the ACIP’s decisions, Walensky puts the booster efforts more in line with the Biden administration’s preliminary plans to offer booster doses to all vaccinated adults, starting this week.

Still, the current recommendations only apply to the Pfizer/BioNTech vaccine and those who received that vaccine for their two-dose “primary series.” Those who initially received two doses of the Moderna COVID-19 vaccine or one shot of Johnson & Johnson’s vaccine are advised to wait for further booster data and recommendations.

For now, here are the CDC’s official recommendations of who should get a Pfizer/BioNTech vaccine booster—to be given at least six months after the primary Pfizer/BioNTech series. (Emphasis added by CDC).

  • people 65 years and older and residents in long-term care settings should receive a booster shot of Pfizer-BioNTech’s COVID-19 vaccine at least 6 months after their Pfizer-BioNTech primary series,
  • people ages 50–64 years with underlying medical conditions should receive a booster shot of Pfizer-BioNTech’s COVID-19 vaccine at least 6 months after their Pfizer-BioNTech primary series,
  • people ages 18–49 years with underlying medical conditions may receive a booster shot of Pfizer-BioNTech’s COVID-19 vaccine at least 6 months after their Pfizer-BioNTech primary series, based on their individual benefits and risks, and
  • people ages 18-64 years who are at increased risk for COVID-19 exposure and transmission because of occupational or institutional setting may receive a booster shot of Pfizer-BioNTech’s COVID-19 vaccine at least 6 months after their Pfizer-BioNTech primary series, based on their individual benefits and risks.
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