Biology

CD4 occupancy triggers sequential pre-fusion conformational states of the HIV-1 envelope trimer with relevance for broadly neutralizing antibody activity

PLOS Biology (new articles) - чт, 2019-01-17 00:00

by Branislav Ivan, Zhaozhi Sun, Harini Subbaraman, Nikolas Friedrich, Alexandra Trkola

During the entry process, the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) trimer undergoes a sequence of conformational changes triggered by both CD4 and coreceptor engagement. Resolving the conformation of these transient entry intermediates has proven challenging. Here, we fine-mapped the antigenicity of entry intermediates induced by increasing CD4 engagement of cell surface–expressed Env. Escalating CD4 triggering led to the sequential adoption of different pre-fusion conformational states of the Env trimer, up to the pre-hairpin conformation, that we assessed for antibody epitope presentation. Maximal accessibility of the coreceptor binding site was detected below Env saturation by CD4. Exposure of the fusion peptide and heptad repeat 1 (HR1) required higher CD4 occupancy. Analyzing the diverse antigenic states of the Env trimer, we obtained key insights into the transitions in epitope accessibility of broadly neutralizing antibodies (bnAbs). Several bnAbs preferentially bound CD4-triggered Env, indicating a potential capacity to neutralize both pre- and post-CD4 engagement, which needs to be explored. Assessing binding and neutralization activity of bnAbs, we confirm antibody dissociation rates as a driver of incomplete neutralization. Collectively, our findings highlight a need to resolve Env conformations that are neutralization-relevant to provide guidance for immunogen development.
Категории: Biology, Journals

Engineered bacteria could mop up toxic ammonia in the human gut

Genetics - ср, 2019-01-16 21:00
Toxic ammonia can build up in the guts of people with certain disorders – probiotics containing bacteria engineered to break down the toxin could help
Категории: Biology

Robot dog taught itself to get back up when people kick it over

Genetics - ср, 2019-01-16 21:00
The ANYmal robot is about the size of a large dog. AI has taught it to stand up after being pushed over by researchers
Категории: Biology

Manatees, whales and turtles are coming back from the brink in the US

Genetics - ср, 2019-01-16 21:00
The Trump administration has plans to weaken a key environmental law, but it has helped many marine animals avoid extinction
Категории: Biology

Growth of desalination plants is a serious problem for marine life

Genetics - ср, 2019-01-16 20:00
The super salty waste water dumped into the oceans by the world’s 16,000 desalination plants can push marine species beyond what they can tolerate
Категории: Biology

Type 2 diabetes may not be a lifelong condition

Genetics - ср, 2019-01-16 20:00
New evidence shows that weight loss can push the condition into remission, offering hope for patients, says Elizabeth Robertson
Категории: Biology

Robot version of our distant ancestor hints at how we learned to walk

Genetics - ср, 2019-01-16 20:00
A robotic version of a four-legged animal that lived 290 million years ago suggests it had an efficient walking style despite spending some of its life in water
Категории: Biology

The Dream review – a podcast tale of how firms manipulate our brains

Genetics - ср, 2019-01-16 20:00
A shocking podcast tells the story of how poor people are being exploited by new kinds of companies that have turned the insights of cognitive science on them
Категории: Biology

'We'll die before we find the answer': Crisis at the heart of physics

Genetics - ср, 2019-01-16 20:00
Ambitious new theories dreamed up to explain reality have led us nowhere. Meet the hardcore physicists trying to think their way out of this black hole
Категории: Biology

Why doing more exercise won't help you burn more calories

Genetics - ср, 2019-01-16 20:00
Forget the idea that to lose weight you just need to work off more calories than you consume. The truth is far weirder
Категории: Biology

Huge spinning ice disc in river provides a carousel for ducks

Genetics - ср, 2019-01-16 18:57
Residents of Westbrook in Maine discovered an enormous circle of ice slowly spinning in the Presumpscot river running through their city
Категории: Biology

The war against antibiotic resistance is finally turning in our favour

Genetics - ср, 2019-01-16 18:53
We are finally seeing progress in the battle against antibiotic resistance, but now we must make it profitable to develop new drugs
Категории: Biology

Behind the Sheet review – Slave women's painful gift is honoured

Genetics - ср, 2019-01-16 18:44
The story of the unsung slave women who helped end an excruciating condition by enduring surgery without anaesthetic makes a play that deserves a wide audience
Категории: Biology

New Scientist launches internship scheme for aspiring BAME journalists

Genetics - ср, 2019-01-16 18:20
To boost diversity in science journalism, we’re launching a training internship for aspiring journalists from Black, Asian and Minority Ethnic backgrounds
Категории: Biology

Cuttlefish embryos can see and recognise predators before they hatch

Genetics - ср, 2019-01-16 17:48
The transparent eggs of pharaoh cuttlefish let them see predators long before they hatch and they can even learn to spot new threats
Категории: Biology

Thousands of Elite Dangerous players embark on epic space voyage

Genetics - ср, 2019-01-16 15:04
What exciting discoveries await the Elite Dangerous mission to the Milky Way’s outer edges? It’s not run by NASA but the epic sciencey game feels like the real deal
Категории: Biology

Long lost cities in the Amazon were once home to millions of people

Genetics - ср, 2019-01-16 14:00
We used to think the Amazon rainforest was virtually untouched, but it now seems to have been filled with sprawling settlements whose inhabitants shaped the land
Категории: Biology

China's moon garden is dead as the craft is plunged into lunar night

Genetics - ср, 2019-01-16 13:47
Cotton seeds growing on China's Chang'e 4 probe on the far side of the moon have been plunged into darkness, marking the end of the first lunar biosphere experiment
Категории: Biology

Long penises help hermit crabs avoid being robbed during sex

Genetics - ср, 2019-01-16 02:01
Some male hermit crabs have unusually long penises. This could be so that they can protect their homes whilst having sex
Категории: Biology

How hagfish can make enough slime to clog a shark's jaws in seconds

Genetics - ср, 2019-01-16 02:01
Hagfish use slime to clog up sharks’ jaws in milliseconds, and it’s the water drag generated when the shark inhales that helps the slime form so quickly
Категории: Biology