Vol 451 | Issue no. 7177 | 24 January 2008 AUTHORS

Abstractions MAKING THE PAPER LAST AUTHORS Paul Bieniasz Lithium and beryllium are the first metals encountered in the periodic table, but these elements do not bond to one another Unravelling a mechanism that stops — at least, not under ambient conditions. On HIV travelling between cells. page 445, renowned theoretical physicist Neil Ashcroft and Nobel-prize-winning pose a major threat to the fit- chemist Roald Hoffmann, both at Cornell ness and survival of many animals, including University in Ithaca, New York, report using humans. Researchers have now identified a computational methods to demonstrate that factor that keeps one type of the most noto- an alloy of these two metals, with unusual rious human , HIV-1, stuck to the quantum behaviour, could be created at high surface of human cells and unable to spread. pressures. They spoke to Nature about how HIV-1 encodes a slew of , and relies bridging disciplines opens new frontiers. on host cells’ machinery to make them. Among Does chemistry have a role in quantum these is a set of accessory proteins that for some went away”. Although initially disappointing, the physics? time didn’t seem to be important for rep- results ultimately provided a key piece of infor- NA: The periodic table was created from lication. One of these, Vpu, allows the virus to mation. When cells are transfected with ‘dirty’ an understanding of how elements react at escape from the external surface of cells. HIV-1 DNA, they sometimes produce and ambient pressure. Now we need a greater that lack Vpu get stuck, and cannot other cytokines as part of an immune response. understanding of how the chemistry, as leave cells to invade others. Bieniasz and Neil realized that the they well as quantum physics, of elements in Paul Bieniasz, a virologist at the Aaron Dia- were looking for was not ICAM-1, but one that combination changes under pressure. mond AIDS Research Center and Laboratory could be induced by interferon. RH: For me, this was a chance to convince of Retrovirology at The After a series of experiments failed to isolate physicists that chemists also understand in New York, and his group began scouring the the mystery protein, the researchers reluctantly bonding. literature for cell-surface proteins that might shifted strategy. They decided to compare hold on to HIV-1 in the absence of Vpu. They expression in various cell lines, treating some What initial findings led to this paper? thought that Vpu might function by antago- of them with interferon-α. But they were pes- NA: No one thought a light alkali metal could nizing such a protein — which they dubbed simistic: “We thought there would be too many ever be a superconductor until, in 1997, tetherin — allowing the virus to escape. candidates to weed through,” says Bieniasz. my group found that lithium could be at The search led the team to an adhesion Instead, the results were “quite stunning”, with extremely low temperatures. Then we found molecule known as ICAM-1. “We knew that fewer than 10 candidate meeting their that by putting lithium under high pressure, tetherin made the cell surface sticky, so a good selection criteria (see page 425). the superconducting temperature could be candidate for that would be a cell-adhesion Once the gene-expression data were in hand, quite high. More recently, we wondered why molecule,” says Bieniasz. Earlier research had the story unfolded very quickly. The team iden- beryllium, lithium’s neighbour, is not a better superconductor. We decided to see whether shown that ICAM-1 could be incorporated tified a favourite candidate within an hour, and forming a beryllium–lithium alloy improved its into HIV particles. the protein a week later. “It was very satisfying,” chances. Our computations suggest some of Stuart Neil, then a postdoctoral researcher in Bieniasz says. the alloys are stable at higher pressures, and Bieniasz’s laboratory, was keen to get to work. There is still much to learn about tetherin, they may even be good superconductors. He quickly cloned ICAM-1 and introduced it however. There are hints that the protein has and HIV-1 to cells. ICAM-1 seemed to inhibit broad antiviral activity, yet few viruses make How might the alloy be useful? the release of the viral particles, an effect that Vpu, which suggests that they have some other RH: Unfortunately, it is not inherently useful the addition of Vpu could counteract. way of skirting tetherin’s stickiness. Bieniasz also — but then, neither was E = mc2 at first. The But, says Bieniasz, when Neil, now a lecturer wonders whether genetic variation in tetherin world has a way of making new ideas useful. at King’s College London, repeated the same might affect susceptibility to HIV infection or We gain insight into the nature of chemical experiment using ICAM-1 DNA that had been other viral diseases. So there’s plenty of work to bonds when we are able to make new more thoroughly purified, “the effect completely keep him tethered to the lab bench. ■ compounds — in this case using pressure.

This paper was the work of one student and three professors. How did each of you FROM THE BLOGOSPHERE contribute? Welcome to Indigenus, the replies, Bikash Mohanty many budding scientists who RH: We didn’t know what structural latest member of the NPG writes that much published can’t afford to knock on the combinations were possible between lithium blogosphere! It is the blog of Indian research is repetition doors of NIH and Wellcome and beryllium, so graduate student Ji Feng the equally new portal Nature of the work done in “so called Trust”. In addition, Chokkappa explored structures based on known chemical India (http://www.nature.com/ scientifically advanced believes that Nature India could and physical rules while our colleague Richard Hennig searched random combinations for nindia/), a one-stop site for countries”. He thinks Nature help advance careers by putting specific characteristics. Neil and I provided information on Indian science. India should highlight original ambitious students in touch physical and chemical explanations for In her inaugural post, Subhra Indian research. with established scientists. the findings — particularly the unusual Priyadarshini, editor of Nature Arun Kumar Chokkappa Vinod Jyothikumar hopes two-dimensional electronic structures that India, asks Indigenus readers suggests Nature India lists and that the Nature India portal will emerged when modelled alloys were being what content Nature India tracks the funding opportunities result in more international squeezed in three dimensions. In the end, should provide (http://tinyurl. that exist in the region, which collaborators becoming it was Ji that came up with the theoretical com/3ba74g). Among the “would be an eye opener for so interested in research in India. ■ quantum mechanical model used in the paper Visit Nautilus for regular news relevant to Nature authors ➧ http://blogs.nature.com/nautilus and see to explain these structures. ■ Peer-to-Peer for news for peer-reviewers and about peer review ➧ http://blogs.nature.com/peer-to-peer.

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