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Scientists Find New Metabolic Pathways to Resist Viruses

10-10-2016

International partnership unravels the mechanism by which Hepatitis C Virus (HCV) reprograms human metabolism, and identifies new pathways of anti-viral resistance

Viral infection is one of the leading medical challenges of the 21st Century, ranging from the Hepatitis C Virus (HCV) epidemic affecting 3% of the global population, to recent outbreaks of West Nile, Zika, and Ebola viruses.

Viruses are parasites that lack the basic metabolic machinery needed to replicate. To get around this problem, they hijack the metabolic machinery of their hosts in order to complete their life cycle and propagate. However, scientists still don’t have a good understanding of the metabolic interplay between viruses and the organisms they infect. This is mainly due to the complex interplay between human genes and metabolic processes.

Now, in new research appearing in the journal Nature Chemical Biology, an international research group led by the Hebrew University of Jerusalem systematically identified an array of genetic switches that controls the metabolic response to Hepatitis C Virus infection. By carefully selecting drugs that target these genetic switches, the researchers were able to show how these genes control metabolic processes, such as glucose and lipid metabolism, and establish how these processes affect the virus lifecycle. Surprisingly, while some metabolic processes were beneficial for the virus, for example by providing it with building blocks for its genetic material allowing it to replicate faster, other metabolic processes were surprisingly anti-viral, disturbing the viral lifecycle.

“This is the first indication that our cells can block replication of Flaviviridae viruses like HCV and Zika by denying them from critical building blocks the viruses need to survive,” said Prof. Yaakov Nahmias, Director of the Alexander Grass Centre for Bioengineering at the Hebrew University of Jerusalem, who led the study. “Our results present a new approach to treat virus infection by targeting the genetic regulation of metabolic processes on which the virus rely.”

Nuclear Receptors

Metabolism is a complex phenomenon that is primarily regulated by genetic switches called nuclear receptors. Nuclear receptors are a family of proteins found within cells that are activated by metabolites such as fatty acids or glucose, acting as sensors that allow cells to sense and respond to changes in nutrition (e.g. breakfast) by regulating the expression (i.e. activation) of hundreds of genes.

Viruses such as HCV can interfere with this metabolic regulation. When this happens, it results in fatty liver disease and diabetes in infected patients.

To find the mechanism by which viruses such as HCV can interfere with metabolic regulation, the researchers used a new laboratory model of human liver cells developed by Prof. Nahmias. By mapping out the metabolism of both infected liver cells and normal liver cells, they were able to focus on disturbed metabolic processes, and identify the nuclear receptors responsible for their dysregulation.

“This is a fascinating approach,” said Prof. Oren Shibolet, head of the Department of Gastroenterology at Tel Aviv Sourasky Medical Centre and Tel-Aviv University and a co-author of the study, “as the same methodology can be applied to study the metabolic regulation of liver cancer and other infections to possibly identify new therapeutic targets.”

Once the researchers identified the genetic switches controlling the disturbed metabolic processes, they blocked each nuclear receptor using pharmaceuticals, and studied the effects of this inhibition on the virus. While blocking glucose metabolism was detrimental to the virus, blocking lipid metabolism had the reverse effect, actually increasing HCV replication. These findings were validated in a small cohort of HCV patients.

The authors point out that the Flaviviridae family of viruses, which includes Hepatitis C, Dengue, West Nile, Yellow Fever, and Zika viruses, were previously considered to be expert metabolic engineers that optimized the hijacking of host metabolic machinery to create more viruses. “It was quite surprising to see that human liver cells could use metabolic processes to resist viral infection,” said Prof. Jörg Timm, a co-author from the Institute of Virology at the University of Düsseldorf. “It went against our common understanding of viruses as expert metabolic engineers, suggesting new avenues to target virus infection.”  

Participating institutions include The Hebrew University of Jerusalem, Harvard Medical School, Broad Institute of MIT and Harvard, Tel Aviv University, University Duisburg-Essen, and the University of Düsseldorf

Latin American Academic Leaders Visit Israel, Sign Cooperation Agreements with Hebrew University

Some twenty rectors from leading Latin American universities visited Israel this week and signed agreements with the Hebrew University of Jerusalem, in a first-of-its-kind conference signalling growing academic cooperation

15-12-2016

Higher BMI in Adolescence May Affect Cognitive Function in Midlife

Study of Israeli adolescents also looks at impact of socioeconomic position on subsequent cognitive impairment

08-12-2016

A New Passion Fruit Variety Keeps the Brain Young

Hebrew University Researchers Develop a New Strain of Passion Fruit that significantly protects brain cells and its function from aging-related damage

08-12-2016

Best History Book France 2016

A history book about Jewish-Arab relations titled Juifs et musulmans en Palestine et en Israel des origines à nos jours recently won the first prize for the best history book published in France in 08-12-2016

Hebrew University Congratulates Researchers On Receiving 2016 EMET Prize

Hebrew University Researchers Bring Home 3 of the 8 EMET Prizes Awarded for 2016

04-12-2016

The Bert and Ernie Principle of Sharing:

When and Why Do Children Give Others the Bigger Piece of the Pie?

29-11-2016

Researchers uncover a survival mechanism in cancer cells

Scientists from the Crick Institute, London and the Hebrew University, Jerusalem, discover a protein that plays a key role in turning cancer tumour cells into cancer stem cells that are able to renew outbreaks of the disease

22-11-2016

Hebrew University Students Ranked the 67th Most Employable Worldwide

An analysis of graduates employability published by Times Higher Education (THE) has ranked graduates of the Hebrew University of Jerusalem as the 67th most employable in the world.

20-11-2016

Canada's Governor General Visits Hebrew University's Faculty of Medicine

Governor General discusses collaborative medical research partnerships between Canada and Israel at IMRIC, the Institute for Medical Research Israel-Canada

03-11-2016

Italian President Sergio Mattarella Visits the Hebrew University of Jerusalem

On the first day of his state visit to Israel, the President of the Italian Republic, Sergio Mattarella, gave a keynote address to an overflow audience, at the Truman Institute on the university's Mount Scopus campus.

30-10-2016

The Hebrew University European Brain Forum 'Brain & Pain'

Sunday 20th November: 10:30 - 17:00 Paris

27-10-2016

Strategic Partnership between the Hebrew University and the University of Vienna

Four joint seminars took place, where scientists from the Hebrew University and the University of Vienna met to exchange ideas and to prepare proposals for third party funding

27-10-2016

Limmud Conference 2016

Deborah Steinmetz, Director, Steven Spielberg Jewish Film Archive

18-10-2016

Scientists Find New Metabolic Pathways to Resist Viruses

International partnership unravels the mechanism by which Hepatitis C Virus (HCV) reprograms human metabolism, and identifies new pathways of anti-viral resistance

10-10-2016

Groundbreaking Immune Approach Targets Humans Instead of Bacteria

Scientists show for the first time how bacterial superantigen toxins work, and how short peptides can block them and save lives

06-10-2016

Asian Religious Leaders Discuss Peace, Environment With Israeli Counterparts at Hebrew University

A delegation of Asian religious leaders visited the Hebrew University of Jerusalem

13-09-2016

Hebrew University Launches Israel’s First Academic Degree Programme in Viticulture and Enology

Innovative boutique programme for professional training in the growth, production and analysis of wine, as well as wineries management

17-08-2016

New Chair of the Young Professionals Group

Succeeding Jacqueline Caspi as Chair of the BFHU Young Professional Committee is Benjamin Stowe

16-08-2016

Rare Frescoes from Roman Period Discovered in Hebrew University Excavations at Zippori in Galilee

New finds contribute significantly to research of Roman art in Israel: Provide first evidence of figurative images in wall paintings at the site, and precede earliest mosaics discovered at the site by a hundred years

10-08-2016

Historic Find at Tel-Hazor: A Statue of an Egyptian Official

In a historic find, a large fragment of an Egyptian statue measuring 45 X 40 centimetres, made of lime-stone, was discovered In the course of the current season of excavations at Tel-Hazor, north of the Sea of Galilee in Israel

25-07-2016

IMRIC Scientist Awarded for Work in Stem Cells & Regenerative Medicine

Dr. Yosef Buganim is a young researcher at the Institute for Medical Research Israel-Canada (IMRIC), part of the Hebrew University's Faculty of Medicine

18-07-2016

Single Dose of Novel Peptide Protects Cognitive Function after Mild Traumatic Brain Injury

New molecules, developed by Hebrew University of Jerusalem scientists, reduce inflammation, cell death and cognitive impairments following traumatic brain injury in mice

11-07-2016

Hebrew University #1 in Middle East, #26 Worldwide, Says Saudi-based Centre

The Centre for World University Rankings (CWUR), based in Saudi Arabia, has ranked the Hebrew University of Jerusalem at #26 among the 25,000+ degree-granting institutions in the world.

11-07-2016

European Neuroscience Outreach Award

Goes to Hebrew University's ELSC Brain Sciences Centre

07-07-2016

Dame Helen Mirren Meets Arab and Jewish Students at Hebrew University

Dame Helen Mirren, one of the world's best-known and most respected actresses, met with Arab and Jewish theatre students at The Billy Crystal Program for Peace Through the Performing Arts

26-06-2016

Hebrew University Ranked #17 in Asia, First in Israel, in 2016

Times Higher Education Asia University Rankings Editor of Times Higher Education Rankings: "It has never been as clear to me that the balance of power is shifting from the West to the East."

20-06-2016

Prof. Rina Talgam Awarded the Polonsky Prize

Historical survey of excavated mosaic art of pagans, Jews, Samaritans, Christians and Muslims earns Hebrew University professor the first prize in this year's Polonsky Awards

08-06-2016

A New Immunotherapy against Cancer Earns a Hebrew University Researcher the Kaye Innovation Award

Pinchas Tsukerman developed a novel immunotherapy method in which monoclonal antibodies neutralize the tumor's ability to suppress the immune system

07-06-2016

Israeli President Reuven Rivlin at Hebrew University Convocation:

'Striving to expand the government is correct and justified.' President Rivlin, a Hebrew University alumnus, praises academia's role as unifier of Israeli society

29-05-2016

Young Professional Group hosted a dinner in the House of Lords

The British Friends of The Hebrew University Young Professional Group has held its first dinner. The dinner was hosted by Lord Pannick QC in the Peers' Dining Room, House of Lords

26-05-2016

President Rivlin, a Hebrew University alumnus, to deliver keynote address

Israeli President Reuven Rivlin, American Jewish Philanthropist Mortimer B. Zuckerman, and i24 founder Patrick Drahi To Be Honored at Hebrew University Convocation

22-05-2016

University of Toronto and the Hebrew University of Jerusalem Deepen Ties

The University of Toronto and The Hebrew University of Jerusalem are pleased to deepen their partnership in the fields of social work and bio-innovation

19-05-2016

Prime Minister of Singapore Begins Official Visit to Israel at the Hebrew University of Jerusalem

Hebrew University signs agreements with leading academic institutions from the Republic of Singapore, and confers honorary doctorate upon Prime Minister Lee Hsien Loong

18-04-2016

New Human On Chip Technology Permits Unparalleled Insight into the Dynamics of Cellular Function

Hebrew University's liver-on-chip platform is uniquely able to monitor metabolic changes indicating mitochondrial damage occurring at drug concentrations previously regarded as safe

04-04-2016

Yissum Showcases Hebrew University’s Breakthroughs in Advanced Materials and Nanotechnology

Yaacov Michlin, CEO, Yissum: During 2015, Yissum founded a record number of eight companies based on inventions of researchers from the Hebrew University Centre for Nanoscience and Nanotechnology

31-03-2016

President Pavlopoulos of Greece Awarded Hebrew University Honorary Doctorate

His Excellency the President of the Hellenic Republic, Mr. Prokopios Pavlopoulos, was awarded an honorary doctorate by the Hebrew University of Jerusalem.

30-03-2016

Yissum takes part in project to Operate a Tech Incubator under Israel's National Incubator Programme

Jerusalem Venture Partners (JVP) LED Group joins forces with Motorola Solutions (NYSE: MSI), Reliance Industries (NSE: Reliance) and Yissum, the Research Development Company of the Hebrew University of Jerusalem

22-03-2016

Scientists Generate a New Type of Human Stem Cell That Has Half a Genome

The haploid stem cells may yield new genetic screening tools and therapies

16-03-2016

New method detects multiple diseases via DNA released from dying cells into blood

New blood test uses methylation patterns of circulating DNA from dying cells to detect diabetes, multiple sclerosis, pancreatic cancer, pancreatitis and brain damage, opening up vast possibilities for diagnostic medicine.

14-03-2016

Yissum

The Technology Transfer Company of the Hebrew University, comes to London

10-03-2016

The Hebrew University of Jerusalem to Name School of Education in Honour of Former Head Seymour Fox

Dedication Ceremony and Memorial Lecture on March 14 on Mount Scopus

10-03-2016

New Device Shortens Chest-Tube Insertion From Minutes To Seconds

Hebrew University students develop life-saving device following a wave of stabbing attacks that leaves some civilians with collapsed lungs

09-03-2016

Cellular Aging Process Unexpectedly Enhances Insulin Secretion

Researchers find that a cell aging program causes human and mouse pancreatic beta cells to work harder and secrete more insulin

07-03-2016

Scientists "break the ice" on organ banking

Hebrew University researchers develop a solution for long-term preservation of cells and organs for transplant, as part of a global alliance to bank organs

02-03-2016

Nanotechnology delivery system offers new approach to skin disease therapies

Hebrew University formula that activates the body's natural defense against free radicals could control a variety of skin pathologies and disorders

29-02-2016

Optical Guide Aims To Keep Orthopaedic Procedures Right On Target

New fibre optic guide-wire will enable surgeons to perform highly accurate hip fracture and spinal fusion surgery with minimal side effects

23-02-2016

Rare Einstein Documents Related To Historic Gravity Announcement Displayed at Hebrew University

Scientists At NSF Press Conference in D.C. Confirm Einstein's Century-Old Prediction

11-02-2016

The 2016 Institute for Law and Policy at The Hebrew University Faculty of Law

Three-Week Summer Program for International Students and Attorneys Opens June 27, 2016

08-02-2016

Hebrew University Linguist Prof. Edit Doron to be Awarded Israel Prize

Israeli Minister of Education Naftali Bennett has announced that Prof. Edit Doron will be awarded the Israel Prize for her work in the study of Linguistics.

03-02-2016

Hebrew University Researchers Led Israel With 14 ERC Grants from EU in 2015

Over 23,000,000 Euros to Promote Groundbreaking Research in Medicine, Mathematics & Sciences, and the Humanities

07-01-2016

The British Friends turn 90 years old!

Supporting the Hebrew University since 1926

05-01-2016
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