Structure of the herpes simplex virus portal-vertex

PLOS Biology (new articles) - 18 hours 46 хв ago

by Marion McElwee, Swetha Vijayakrishnan, Frazer Rixon, David Bhella

Herpesviruses include many important human pathogens such as herpes simplex virus, cytomegalovirus, varicella-zoster virus, and the oncogenic Epstein–Barr virus and Kaposi sarcoma–associated herpesvirus. Herpes virions contain a large icosahedral capsid that has a portal at a unique 5-fold vertex, similar to that seen in the tailed bacteriophages. The portal is a molecular motor through which the viral genome enters the capsid during virion morphogenesis. The genome also exits the capsid through the portal-vertex when it is injected through the nuclear pore into the nucleus of a new host cell to initiate infection. Structural investigations of the herpesvirus portal-vertex have proven challenging, owing to the small size of the tail-like portal-vertex–associated tegument (PVAT) and the presence of the tegument layer that lays between the nucleocapsid and the viral envelope, obscuring the view of the portal-vertex. Here, we show the structure of the herpes simplex virus portal-vertex at subnanometer resolution, solved by electron cryomicroscopy (cryoEM) and single-particle 3D reconstruction. This led to a number of new discoveries, including the presence of two previously unknown portal-associated structures that occupy the sites normally taken by the penton and the Ta triplex. Our data revealed that the PVAT is composed of 10 copies of the C-terminal domain of pUL25, which are uniquely arranged as two tiers of star-shaped density. Our 3D reconstruction of the portal-vertex also shows that one end of the viral genome extends outside the portal in the manner described for some bacteriophages but not previously seen in any eukaryote viruses. Finally, we show that the viral genome is consistently packed in a highly ordered left-handed spool to form concentric shells of DNA. Our data provide new insights into the structure of a molecular machine critical to the biology of an important class of human pathogens.
Категорії: Biology, Journals

Reporters to mark and eliminate basal or luminal epithelial cells in culture and in vivo

PLOS Biology (new articles) - 18 hours 46 хв ago

by Olmo Sonzogni, Jennifer Haynes, Laurie A. Seifried, Yahia M. Kamel, Kai Huang, Michael D. BeGora, Faith Au Yeung, Celine Robert-Tissot, Yujing J. Heng, Xin Yuan, Gerbug M. Wulf, Ken J. Kron, Elvin Wagenblast, Mathieu Lupien, Thomas Kislinger, Gregory J. Hannon, Senthil K. Muthuswamy

The contribution of basal and luminal cells to cancer progression and metastasis is poorly understood. We report generation of reporter systems driven by either keratin-14 (K14) or keratin-8 (K8) promoter that not only express a fluorescent protein but also an inducible suicide gene. Transgenic mice express the reporter genes in the right cell compartments of mammary gland epithelia and respond to treatment with toxins. In addition, we engineered the reporters into 4T1 metastatic mouse tumor cell line and demonstrate that K14+ cells, but not K14− or K8+, are both highly invasive in three-dimensional (3D) culture and metastatic in vivo. Treatment of cells in culture, or tumors in mice, with reporter-targeting toxin inhibited both invasive behavior and metastasis in vivo. RNA sequencing (RNA-seq), secretome, and epigenome analysis of K14+ and K14− cells led to the identification of amphoterin-induced protein 2 (Amigo2) as a new cell invasion driver whose expression correlated with decreased relapse-free survival in patients with TP53 wild-type (WT) breast cancer.
Категорії: Biology, Journals

NASA outlines its plans to deal with a large asteroid impact

Genetics - Ср, 2018-06-20 21:57
NASA is designing and testing missions to deflect a potential asteroid from hitting Earth, and working with emergency responders to plan for a day when one does
Категорії: Biology

Ötzi the Iceman ran out of rock to make his tools before he died

Genetics - Ср, 2018-06-20 21:00
Ötzi the Iceman, a prehistoric man found mummified in a mountain glacier, was short of crucial supplies in the days and weeks before his violent death
Категорії: Biology

Eating less red meat protects against endometriosis

Genetics - Ср, 2018-06-20 17:59
Minimising red meat consumption seems to protect against endometriosis, according to a study of more than 80,000 women who were followed for two decades
Категорії: Biology

Children seized at US border will face lasting health effects

Genetics - Ср, 2018-06-20 16:55
The psychological and physical effects of serious trauma are likely to impact the children being separated from their families at the US border for years
Категорії: Biology

Cocaine in the water makes eels hyperactive and damages muscles

Genetics - Ср, 2018-06-20 15:01
There are low levels of cocaine and other drugs in many rivers, and lab studies suggest that European eels are suffering muscle damage as a result
Категорії: Biology

Consciousness: How we’re solving a mystery bigger than our minds

Genetics - Ср, 2018-06-20 14:00
What is being in love, feeling pain or seeing colour made of? How our brains make conscious experience has long been a riddle – but we’re uncovering clues
Категорії: Biology

The Milky Way has devoured 15 other galaxies since it formed

Genetics - Ср, 2018-06-20 13:15
Our galaxy formed fast, and with an appetite. It’s devoured 15 other galaxies, including a big one nicknamed Kraken that we didn’t know existed until now
Категорії: Biology

Robo bomb squads compete to gather evidence after a drone attack

Genetics - Ср, 2018-06-20 12:52
Obstacle courses, simulated chemical spills, and IEDs are just some of the challenges bomb squads tackle with ground robots and drones at the Robot Rodeo competition
Категорії: Biology

The New York bird with a song that may be a thousand years old

Genetics - Ср, 2018-06-20 12:00
A walk in the Hudson Valley 1000 years ago may have sounded similar to today. A simulation shows the songs passed down by swamp sparrows can last a millennium
Категорії: Biology

Stealth sheets can make you appear invisible to infrared cameras

Genetics - Ср, 2018-06-20 11:00
A cloaking material renders objects almost completely invisible in infrared light and could have military applications
Категорії: Biology

We have hints of a theory beyond quantum physics

Genetics - Ср, 2018-06-20 11:00
If you think our best theory of reality is weird you ain't seen nothing yet, says physicist Ciarán Lee – it could be a fuzzy version of something bigger
Категорії: Biology

Black men are left out of cancer trials because of their biology

Genetics - Ср, 2018-06-20 09:00
Prostate cancer is more common in African Americans, but they are less likely to be included in drug trials. Unintended biological biases are partly to blame
Категорії: Biology

Dietary rescue of lipotoxicity-induced mitochondrial damage in Peroxin19 mutants

PLOS Biology (new articles) - Вт, 2018-06-19 23:00

by Julia Sellin, Christian Wingen, Dominic Gosejacob, Deniz Senyilmaz, Lea Hänschke, Sven Büttner, Katharina Meyer, Daniele Bano, Pierluigi Nicotera, Aurelio A. Teleman, Margret H. Bülow

Mutations in peroxin (PEX) genes lead to loss of peroxisomes, resulting in the formation of peroxisomal biogenesis disorders (PBDs) and early lethality. Studying PBDs and their animal models has greatly contributed to our current knowledge about peroxisomal functions. Very-long-chain fatty acid (VLCFA) accumulation has long been suggested as a major disease-mediating factor, although the exact pathological consequences are unclear. Here, we show that a Drosophila Pex19 mutant is lethal due to a deficit in medium-chain fatty acids (MCFAs). Increased lipolysis mediated by Lipase 3 (Lip3) leads to accumulation of free fatty acids and lipotoxicity. Administration of MCFAs prevents lipolysis and decreases the free fatty acid load. This drastically increases the survival rate of Pex19 mutants without reducing VLCFA accumulation. We identified a mediator of MCFA-induced lipolysis repression, the ceramide synthase Schlank, which reacts to MCFA supplementation by increasing its repressive action on lip3. This shifts our understanding of the key defects in peroxisome-deficient cells away from elevated VLCFA levels toward elevated lipolysis and shows that loss of this important organelle can be compensated by a dietary adjustment.
Категорії: Biology, Journals

A huge number of mystery microbes are living on your skin

Genetics - Вт, 2018-06-19 19:00
We thought we knew about most of the species in our bodies’ microbiomes, but a study has revealed a large number of previously-unidentified organisms
Категорії: Biology

Special cells could let you control your diabetes with coffee

Genetics - Вт, 2018-06-19 18:00
A cup of coffee after a meal might be enough to keep diabetes under control, thanks to caffeine-triggered cells that have been engineered to release insulin
Категорії: Biology

IBM’s debating robot argues it out with human for first time

Genetics - Вт, 2018-06-19 17:21
IBM's AI has taken on humans in a public debate. Though it made some very robot-like errors, the AI won one debate and lost the other, based on a crowd vote
Категорії: Biology

Alien preppers could hoard stars to survive in a doomed universe

Genetics - Вт, 2018-06-19 16:46
Dark energy is accelerating the expansion of the universe, meaning eventually all galaxies will be inaccessible, but aliens could be working on a solution right now
Категорії: Biology

Why video-assisted referees won’t stop World Cup errors

Genetics - Вт, 2018-06-19 15:00
The football tournament kicking off this week is introducing video replays for key calls. Human psychology means some decisions will improve – but some won't
Категорії: Biology