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HIV: Seeking ultimate victory

Nature - Wed, 01/07/2015 - 01:00

HIV: Seeking ultimate victory

Nature 517, 7534 (2015). doi:10.1038/nature14194

Authors: Louis J. Picker & Jeffrey D. Lifson

HIV variants that have mutated to escape T-cell immune responses dominate the latent viral reservoir in most patients on antiretroviral therapy. This finding will need to guide therapeutic approaches targeting reactivated virus. See Letter p.381

Categories: Literature

Broad CTL response is required to clear latent HIV-1 due to dominance of escape mutations

Nature - Wed, 01/07/2015 - 01:00

Broad CTL response is required to clear latent HIV-1 due to dominance of escape mutations

Nature 517, 7534 (2015). doi:10.1038/nature14053

Authors: Kai Deng, Mihaela Pertea, Anthony Rongvaux, Leyao Wang, Christine M. Durand, Gabriel Ghiaur, Jun Lai, Holly L. McHugh, Haiping Hao, Hao Zhang, Joseph B. Margolick, Cagan Gurer, Andrew J. Murphy, David M. Valenzuela, George D. Yancopoulos, Steven G. Deeks, Till Strowig, Priti Kumar, Janet D. Siliciano, Steven L. Salzberg, Richard A. Flavell, Liang Shan & Robert F. Siliciano

Despite antiretroviral therapy (ART), human immunodeficiency virus (HIV)-1 persists in a stable latent reservoir, primarily in resting memory CD4+ T cells. This reservoir presents a major barrier to the cure of HIV-1 infection. To purge the reservoir, pharmacological reactivation of latent HIV-1 has been proposed and tested both in vitro and in vivo. A key remaining question is whether virus-specific immune mechanisms, including cytotoxic T lymphocytes (CTLs), can clear infected cells in ART-treated patients after latency is reversed. Here we show that there is a striking all or none pattern for CTL escape mutations in HIV-1 Gag epitopes. Unless ART is started early, the vast majority (>98%) of latent viruses carry CTL escape mutations that render infected cells insensitive to CTLs directed at common epitopes. To solve this problem, we identified CTLs that could recognize epitopes from latent HIV-1 that were unmutated in every chronically infected patient tested. Upon stimulation, these CTLs eliminated target cells infected with autologous virus derived from the latent reservoir, both in vitro and in patient-derived humanized mice. The predominance of CTL-resistant viruses in the latent reservoir poses a major challenge to viral eradication. Our results demonstrate that chronically infected patients retain a broad-spectrum viral-specific CTL response and that appropriate boosting of this response may be required for the elimination of the latent reservoir.

Categories: Literature

Reasons to be cheerful

Nature - Wed, 01/07/2015 - 01:00

Reasons to be cheerful

Nature 517, 7533 (2015). doi:10.1038/517121a

As two new fronts in the war on disease demonstrate, creativity remains a key weapon for scientists in the hunt for drugs.

Categories: Literature

Listen up

Nature - Wed, 01/07/2015 - 01:00

Listen up

Nature 517, 7533 (2015). doi:10.1038/517121b

Human echolocation kicks off the Nature podcast’s new series on sound science

Categories: Literature

Economic divide taking toll on European science

Nature - Wed, 01/07/2015 - 01:00

Economic divide taking toll on European science

Nature 517, 7533 (2015). http://www.nature.com/doifinder/10.1038/517123a

Author: Colin Macilwain

The Horizon 2020 programme threatens to siphon away the best scientists from southern Europe, argues Colin Macilwain.

Categories: Literature

Climate-change biology: Salmon adapt to warmer waters

Nature - Wed, 01/07/2015 - 01:00

Climate-change biology: Salmon adapt to warmer waters

Nature 517, 7533 (2015). doi:10.1038/517124a

Pacific chinook salmon stand a good chance of adapting to higher temperatures in a scenario with modest warming, but could be wiped out under projections of maximum warming.Bryan Neff at the University of Western Ontario in London, Canada, and his colleagues exposed the offspring

Categories: Literature

Engineering: Muscle sensor controls robot arm

Nature - Wed, 01/07/2015 - 01:00

Engineering: Muscle sensor controls robot arm

Nature 517, 7533 (2015). doi:10.1038/517124b

A robot arm can mimic the movements of a human one, thanks to a device that measures muscle activity.Muscle sensors are typically embedded in the tissue, but the flexible device created by Ifor Samuel and his colleagues at the University of St Andrews, UK,

Categories: Literature

Structural biology: Cold drug fits in virus's pocket

Nature - Wed, 01/07/2015 - 01:00

Structural biology: Cold drug fits in virus's pocket

Nature 517, 7533 (2015). doi:10.1038/517124c

An antiviral drug developed for the common cold could be effective against another virus that affected more than 1,000 US children in 2014.An enterovirus called EV-D68 caused respiratory illness, sometimes severe, in an outbreak last August. Michael Rossmann and his colleagues at Purdue University

Categories: Literature

Human evolution: Light bones linked to less activity

Nature - Wed, 01/07/2015 - 01:00

Human evolution: Light bones linked to less activity

Nature 517, 7533 (2015). doi:10.1038/517124d

Low-density bones evolved only relatively recently in modern humans as they shifted from foraging to agriculture and became more sedentary, according to two studies.Habiba Chirchir of the Smithsonian Institution in Washington DC, Brian Richmond of the American Museum of Natural History in New York

Categories: Literature

Developmental biology: Cells stop dividing to heal wounds

Nature - Wed, 01/07/2015 - 01:00

Developmental biology: Cells stop dividing to heal wounds

Nature 517, 7533 (2015). doi:10.1038/517125a

Researchers have worked out why cells that stop dividing often release inflammatory signals that are linked to various age-related disorders.Cells enter this 'senescent' state as tissues age, but it is not clear why they secrete numerous molecules, some of which cause inflammation. Judith Campisi

Categories: Literature

Neuroscience: Direct route from gut to brain

Nature - Wed, 01/07/2015 - 01:00

Neuroscience: Direct route from gut to brain

Nature 517, 7533 (2015). doi:10.1038/517125b

Cells in the intestine can directly communicate with nerves, suggesting a way in which food and gut bacteria might affect the brain.Intestinal cells called enteroendocrine cells regulate feeding behaviour, affecting the brain indirectly by secreting hormones. But these cells also have a protrusion called

Categories: Literature

Immunology: Fat cells fight bacterial infection

Nature - Wed, 01/07/2015 - 01:00

Immunology: Fat cells fight bacterial infection

Nature 517, 7533 (2015). doi:10.1038/517125c

When a pathogenic bacterium invades the skin, fat cells are enlisted to help to kill the microbe, finds a study in mice.Richard Gallo at the University of California, San Diego, and his team studied fat cells beneath the skin of mice that had been

Categories: Literature

Stem cells: Diabetes reversed after transplant

Nature - Wed, 01/07/2015 - 01:00

Stem cells: Diabetes reversed after transplant

Nature 517, 7533 (2015). doi:10.1038/517125d

Therapies that block part of the immune response in diabetic mice can prevent rejection of transplanted cells made from stem cells.Some people with severe type 1 diabetes receive transplants of insulin-producing cells from healthy donors, but must take drugs that suppress much of the

Categories: Literature

Population genetics: Small numbers led to lemur demise

Nature - Wed, 01/07/2015 - 01:00

Population genetics: Small numbers led to lemur demise

Nature 517, 7533 (2015). doi:10.1038/517125e

The number of giant lemurs in Madagascar may have been low even before humans pushed them to extinction.Living lemur populations are found only in Madagascar, with the heaviest species weighing at most 7 kilograms. Giant species weighed up to 160 kg and vanished from

Categories: Literature

Seven days: 2–8 January 2015

Nature - Wed, 01/07/2015 - 01:00

Seven days: 2–8 January 2015

Nature 517, 7533 (2015). http://www.nature.com/doifinder/10.1038/517126a

The week in science: Discredited stem-cell findings linked to contamination; NASA balloon mission springs a leak; and US to consider protections for monarch butterfly.

Categories: Literature

Rave drug holds promise for treating depression fast

Nature - Wed, 01/07/2015 - 01:00

Rave drug holds promise for treating depression fast

Nature 517, 7533 (2015). http://www.nature.com/doifinder/10.1038/517130a

Author: Sara Reardon

Companies and clinicians turn to ketamine to treat mental-health disorder as pipeline of new drugs dries up.

Categories: Literature

Environmental science: Pollution patrol

Nature - Wed, 01/07/2015 - 01:00

Environmental science: Pollution patrol

Nature 517, 7533 (2015). http://www.nature.com/doifinder/10.1038/517136a

Author: Kat Austen

Step aside, fitness trackers. The next wave of personal sensors is giving people the ability to monitor the air they breathe.

Categories: Literature

Mineralogy: Painful extractions

Nature - Wed, 01/07/2015 - 01:00

Mineralogy: Painful extractions

Nature 517, 7533 (2015). doi:10.1038/517142a

Author: Andrew Bloodworth

Andrew Bloodworth weighs up a study revealing the high cost of our technology-driven lust for rare metals.

Categories: Literature

Books in brief

Nature - Wed, 01/07/2015 - 01:00

Books in brief

Nature 517, 7533 (2015). doi:10.1038/517143a

Author: Barbara Kiser

Barbara Kiser reviews five of the week's best science picks.

Categories: Literature

Resources: Silt, dams and hydraulic heroes

Nature - Wed, 01/07/2015 - 01:00

Resources: Silt, dams and hydraulic heroes

Nature 517, 7533 (2015). doi:10.1038/517144a

Author: Philip Ball

A study of China's Yellow River shows how water shapes the nation, finds Philip Ball.

Categories: Literature

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