Virus World

Scientists across the world are closely tracking the spread of mutations in the coronavirus and investigating whether they could render current vaccines less effective. SARS-CoV-2 is no Ferrari among viruses when it comes to mutations. Scientists reckon that its 30,000-base RNA genome acquires around two single-letter mutations a month, a rate around half as fast as influenza and one-quarter the rate of HIV. But allowed to multiply and jump from body to body for more than a year, SARS-CoV-2 has inevitably flourished into a genetically diverse tree branching into countless different variants.  Many variants—defined by a specific assortment of mutations—are relatively unremarkable. But scientists have been keeping a close watch on three rapidly spreading variants—first identified in the UK, South Africa, and Brazil—which harbor an unusual constellation of mutations. They all share a mutation called N501Y that affects the receptor binding domain (RBD) of the spike protein, which the virus uses to clasp onto human cells’ receptors and enter them. That mutation replaces SARS-CoV-2’s 501st amino acid, asparagine, with tyrosine, potentially allowing it to bind more tightly to ACE2 receptors, studies in cells and animal models suggest. By itself, that mutation isn’t unusual, but the variants possess an exceptionally large number of other mutations, some also on the spike protein. Substantive changes to a virus’ behavior, such as heightened transmissibility, are likely the result of multiple mutations rather than individual ones, molecular epidemiologist Emma Hodcroft of the University of Bern tells The Atlantic.  The observation that similar mutations have appeared in three independent variants, and the fact that they are spreading, makes scientists suspect that they may have an evolutionary edge. “They have multiple, eight to ten, mutations in the spike protein all stacked up at once—that suggests that there [is] a lot of evolution and adaption of the protein happening,” Daniel Jones, a molecular pathologist at the Ohio State University, tells The Scientist. “The concern being that since that’s the target of vaccinations and . . . the target for antibody [therapies] like the Regeneron cocktail, for instance, that it might be the beginning of a virus that could evade antibody therapy and/or vaccine coverage.”

SARS-CoV-2 mutations’ effects on transmissibility

It’s often in a virus’ interest to become more transmissible so it can spread and replicate more quickly. Earlier in the pandemic, a spike protein mutation known as D614G—which is widely believed to have made the virus more transmissible—surged to dominance around the world, notes virologist John Moore of Weill Cornell Medical College. Epidemiological data suggest that the B.1.1.7 variant, a descendant of the D614G lineage first identified in the UK that has spread to other parts of the world, also has heightened transmissibility. Eight of the 17 mutations it has recently accumulated are in the spike protein, which could feasibly have an effect on ACE2 binding and virus replication. Hypothetically, if a virus can bind more tightly to the body’s ACE2 receptors, it could be more capable of establishing an infection once it gets into the body and/or of generating more viral particles in the upper respiratory tract, making it easier to transmit to other people, particularly during the presymptomatic stage, explains Theodora Hatziioannou, a virologist at the Rockefeller University in New York. She adds that in her view, it’s hard to definitively ascribe case surges, including the current one in the UK, to single factors such as increased transmissibility, over other driving factors, such as what she sees as ineffective lockdown policies. “I’m not saying that [increased] transmissibility is out of the question. I’m just saying it’s extremely hard to prove.” In South Africa, epidemiologists have estimated that the new variant there, B.1.351 (also known as 501Y.V2), is around 50 percent more contagious compared with dominant lineages, based on its rapid spread, according to The Wall Street Journal. In Brazil, it’s too early to conclude whether a variant now circulating there, called P.1, is inherently more transmissible. First reported on January 12 in the state of Amazonas, it’s been associated with a devastating surge in cases in Manaus, a city where researchers had previously estimated that 75 percent of residents had already been infected with SARS-CoV-2. But it’s still unclear whether properties of the virus itself are contributing to the surge, says virologist Paola Resende of the Oswaldo Cruz Institute in Rio de Janeiro. “In Brazil, we can see a lot of parties, we can see the pubs crowded, and people are on the streets not wearing masks. I think this behavior of the population is the main reason [for] the increase.”

Evading the immune system

Our immune system—and, in particular, antibodies—is a powerful evolutionary force on viruses. Some pathogens such as influenza, and maybe also common cold-causing coronaviruses, mutate their proteins toward new shapes to avoid being targeted by antibodies that would normally prevent them from infecting cells, a process known as antigenic drift. A study recently posted as a preprint to bioRxiv by Hatziioannou and her colleagues suggests that the RBD mutations present in the B.1.351 variant are due to antigenic drift. The team passaged a model virus bearing the dominant SARS-CoV-2 spike protein in the presence of individual neutralizing antibodies extracted from people who had received either the Moderna or Pfizer/BioNTech vaccine. Depending on which antibody they were cultured with, the viruses would gradually adopt a single mutation—either E484K, K417N, and N501Y—which are present in B.1.351. That suggests that “the virus is mutating in these positions to avoid antibodies,” Hatziioannou says. Such antibody-escape mutations don’t necessarily mean that the virus will cause more severe disease or entirely outwit the immune response, she cautions. There are other parts of the immune system to help clear the virus. There’s no evidence so far to suggest that the variants identified in South Africa or Brazil are more lethal. Based on an analysis of several datasets, scientists in the UK suggested last week there’s a “realistic possibility” that B.1.1.7 is deadlier than previous strains, but experts say it’s still too early to draw that conclusion. Another concern is about whether people who have overcome mild infections with older variants could become reinfected with a new one. Nobody that I know has been losing a moment of sleep over the UK variant from a vaccine-efficacy perspective.....

A T cell discovery, "hachimoji" DNA, a new species of human, and mounting fears of espionage rounded off the list this year. 

Discovery of a new T cell

With all the extensive investigations scientists have conducted of the human immune system over the past century, it is astonishing that there are still new cell types to be found. Yet in May, researchers described a hybrid of B and T cells, which they named dual expresser (DE) cells, in people with type 1 diabetes. “We think [the DE cell peptide may play] a very major role during the initial phase of the disease,” Abdel Hamad, an immunologist at Johns Hopkins University School of Medicine and the senior author of the study, told The Scientist at the time. That same month, scientists also reported that humans’ natural killer cells, thought to form the innate immune response, can also keep memories of past encounters with offending antigens, much like the adaptive immune response does. The discovery challenges the basic dogma of how these cells function—another reminder there is still so much unknown even in our own blood.

Infectious diseases spread

Measles, Ebola, and polio flared up in 2019. Cases of measles in the US were the highest since the virus was declared eradicated in America in 2000, and they have been soaring in Europe and elsewhere. Public health officials say insufficient immunization, fueled by anti-vaccine sentiment, is to blame. All the while, scientists continued to learn about the virus—and just how dangerous it is. In October, researchers reported that infection with the virus that causes measles appears to leave the immune system vulnerable to infections by other pathogens. 

Thousands of people died of measles this year in Democratic Republic of Congo, where an outbreak of Ebola has also been ongoing since the 2018. Violence in the region has hampered efforts to get the Ebola epidemic under control, but newly developed drugs and vaccines administered this year may help slow Ebola’s spread.

Polio will soon have another vaccine to contend with as researchers have developed one to designed to counteract the failure of an older vaccine that allowed the virus to continue to circulate and eventually revert to virulence. Such vaccine-derived polio cases have now become more common than those caused by the wild virus, but the new vaccine, which is genetically engineered to avoid such reversion, is set to be deployed in 2020....

First human-monkey chimeras

To “avoid legal issues,” researchers from Spain and the US developed the first human-monkey chimeras in China, a Spanish newspaper reported in July. The embryos’ development was stalled after a few weeks, but the scientists would like to grow animals whose organs could be harvested for human transplant, a goal at least one expert finds impractical. “I always made the case that it doesn’t make sense to use a primate for that. Typically they are very small, and they take too long to develop,” Pablo Ross, a veterinary researcher at the University of California, Davis, told MIT Technology Review.  

While still illegal to pursue in the US using federal research funds, human-animal chimera projects got the regulatory green light in Japan last spring. “It’s good that they now allow people to do human-animal [chimera embryos] with species like pigs and sheep,” Sean Wu, a developmental biologist at Stanford University, told The Scientist in April. But human-primate chimeras are a different, um, animal. “There’s just too many things we don’t know about when you try to chimerize two species that are so close to each other, like humans with nonhuman primates.”....

Scientists are examining the role of T cells, which are likely crucial for long-term protection against SARS-CoV-2. When COVID-19 began spreading like wildfire in the Northeast United States this spring, critical care doctor Nuala Meyer could barely believe what she was seeing. “The number of patients who were presenting with critical illness all at the same time was staggering,” remembers Meyer, a professor of medicine at the Hospital of the University of Pennsylvania. But it wasn’t just that these patients were really sick—it was that they were sick in a startling variety of ways. Some had cardiac issues. Others had blood clots in their legs. Then there were those who developed pneumonia and related respiratory problems. Organ failure affected some. The list went on and on. When Meyer and colleagues profiled the ways in which hospitalized patients’ bodies had tried to combat the virus, they found a variety of different immune responses. T and B cells were highly activated in some but not others, for instance. Their work joins a swath of recent publications aiming to decipher the role of these crucial cells in fending off SARS-CoV-2. To understand how vaccines and long-term immunity function, scientists say, they’ll need to uncover how T and B cells fight this most challenging of infections. In pursuit of this goal, Meyer and her colleagues examined immune responses in a sample of 125 patients. Their findings were published in Science July 15.

The researchers found that some patients had very unbalanced immune cell activity and that this imbalance could manifest in multiple ways. For instance, some produced lots of CD4+ T cells—helper cells that assist other parts of the immune system to block or destroy the virus—but very few CD8+ T “killer” cells, which destroy infected cells in the body. Meanwhile, some patients generated lots of B cells, which churn out antibodies, but not in concert with the two main types of T cell. Getting these cells to work together is important, explains coauthor Michael Betts, an immunologist at the Penn Institute for Immunology, because it helps fight infection on several fronts at once. Some T cells, for instance, help B cells to produce antibodies—it’s a joint effort. In some patients studied by the group, there was a worrying lack of T and B cells in general. Severely ill patients, notably, experienced “the spectrum” of responses, says Betts—from hardly any T and B cell activation to excessive amounts. He says it’s still not clear what drives severe illness in many patients. Scientists also don’t yet know precisely what kind of T and B cell response occurs in patients who have mild or no symptoms....