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(Health) Poxviruses and Lipid Membranes

 
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adedios
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PostPosted: Wed Apr 12, 2006 8:40 am    Post subject: (Health) Poxviruses and Lipid Membranes Reply with quote






Imperial College London
12 April 2006

Novel virus entry mechanism could lead to new drugs against poxviruses

Research published in the Proceedings of the National Academy of Sciences on 11 April describes how the Imperial College London team discovered the mechanism allowing Vaccinia virus to shed its outer lipid membrane and enter cells. The mechanism is unique in virology and paves the way for development of new antiviral drugs.
Many viruses, such as influenza, are surrounded by a single lipid membrane, or envelope, and to enter cells this membrane must be removed. Previously, all enveloped viruses were thought to shed their lipid membrane by fusion with a cell membrane which allows the virus core to be released into the cell.

In contrast, the extracellular form of Vaccinia virus has two lipid membranes, meaning a single fusion event will not release a naked virus core into the cell. The researchers found that interactions between polyanionic or negatively charged molecules on the cell surface and glycoproteins on the virus particle caused a non-fusogenic disruption of the virus outer envelope, allowing the poxvirus to enter the cell.

As well as discovering how the double membrane problem is solved, the researchers demonstrated that polyionic compounds can be used to treat poxvirus infections, even days after infection has started. Disrupting the outer membrane with polyanionic compounds exposes the virus, allowing antiviral antibodies to be more effective. The disruption of the outer membrane also limits the spread of the virus in the body.

Professor Geoffrey L. Smith FRS, from Imperial College London and a Wellcome Trust Principal Research Fellow, said: "This work has uncovered a completely novel biological process. It increases our understanding of how viruses can manipulate biological membranes and will help the development of new drugs against poxviruses, such as variola virus, the cause of smallpox."


###
The research team included Mansun Law, Gemma C. Carter, Kim L. Roberts, Michael Hollinshead and Geoffrey L. Smith.

The researchers have filed a patent for this discovery with Imperial Innovations, the College's spin out arm.

*************************************************************

Questions to explore further this topic:

What is chicken pox?

http://kidshealth.org/parent/i.....n_pox.html
http://kidshealth.org/kid/heal.....n_pox.html
http://www.cdc.gov/nip/disease.....isease.htm
http://www.nlm.nih.gov/medline.....001592.htm
http://www.indiana.edu/~health/chick.html
http://www.intelihealth.com/IH...../9704.html

What is the chicken pox vaccine?

http://www.cdc.gov/nip/vaccine.....accine.htm

What is smallpox?

http://www.nlm.nih.gov/medline.....0_no_0.htm
http://kidshealth.org/kid/heal.....llpox.html
http://kidshealth.org/teen/inf.....llpox.html
http://www.who.int/mediacentre.....allpox/en/
http://www.bt.cdc.gov/agent/sm.....-facts.asp
http://www.hhs.gov/smallpox/
http://www.bt.cdc.gov/Agent/Sm.....Images.asp

What is the smallpox vaccine?

http://www.bt.cdc.gov/agent/sm...../facts.asp
http://www.bt.cdc.gov/agent/sm.....public.asp
http://www.bt.cdc.gov/agent/sm.....tsheet.asp

What is the US government doing to prevent smallpox?

http://www.bt.cdc.gov/agent/sm.....c-prep.asp

Smallpox and movies: fact or fiction

http://www.bt.cdc.gov/agent/sm.....movies.asp

What is the Global Outbreak Response Network of the World Health Organization(WHO)?

http://www.who.int/csr/outbreaknetwork/en/

History of smallpox

http://www.bbc.co.uk/history/d.....x_01.shtml
http://www.cebudoctorsuniversi.....ua163.html

Smallpox and the Philippines

http://www.doh.gov.ph/sphh/balmis.htm
http://www.doh.gov.ph/sphh/1910.htm

Disease prevention and control in the Philippines

http://www.doh.gov.ph/hsra/sur.....ention.pdf

Can smallpox be used as a bioweapon?

http://www.osha.gov/SLTC/smallpox/evaluation.html
http://www.bbc.co.uk/history/w.....n_01.shtml

What are biochemical weapons?

http://www.bbc.co.uk/science/h.....alweapons/

*************************************************************

What are viruses?

http://www.microbe.org/microbes/virus1.asp
http://www.edu.pe.ca/southernkings/microvirus.htm

Are viruses considered living things?

http://www.beyondbooks.com/lif72/2c.asp

An electronic textbook on microbiology

http://www.bact.wisc.edu/Micro.....;book_id=3

A chapter on cell structure and organization

http://www.bact.wisc.edu/Micro.....chap_id=35

A chapter on viral pathogens

http://www.bact.wisc.edu/Micro.....p;secid=13

Images of viruses

http://www.epa.gov/nerlcwww/images.htm

A closer look at viral structures?

http://www-micro.msb.le.ac.uk/109/structure.html
http://micro.magnet.fsu.edu/cells/virus.html
http://gsbs.utmb.edu/microbook/ch041.htm
http://web.uct.ac.za/depts/mmi.....rarch.html

What are the various replication strategies employed by viruses?

http://pathmicro.med.sc.edu/mhunt/dna1.htm

A closer look at virus infection and replication (Herpes Simplex)

http://darwin.bio.uci.edu/%7Ef.....index.html

A closer look at virus infection and replication (Human Immunodeficiency Virus (HIV))

http://www.cellsalive.com/hiv0.htm
http://www.galaxygoo.org/hiv/hiv_lifecycle.html
http://www.pbs.org/wgbh/nova/aids/action.html

A closer look at virus infection and replication (Pox viruses)

http://www.asm.org/microbe/index.asp?bid=40642
http://www.asm.org/microbe/index.asp?bid=40640

What are membranes?

http://www.cytochemistry.net/C.....mbrane.htm
http://medlib.med.utah.edu/NetBiochem/membrane.htm

What are lipids?

http://employees.csbsju.edu/hj.....ntro1.html

What are lipid membranes?

http://www.chori.org/Centers/C.....d_mem.html

Lipid membranes and enveloped viruses

http://www.news.harvard.edu/ga.....virus.html

GAMES

http://medmyst.rice.edu/
http://www.amnh.org/nationalcenter/infection/
http://pbskids.org/cyberchase/games.html


Last edited by adedios on Sat Jan 27, 2007 4:48 pm; edited 2 times in total
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adedios
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PostPosted: Fri Aug 04, 2006 12:50 pm    Post subject: Structure of Smallpox Virus Protein Reply with quote

AUGUST 4, 2006
Penn Researchers Determine Structure of Smallpox Virus Protein Bound to DNA
University of Pennsylvania

Structure Could Aid in Anti-Viral Drug Design

(Philadelphia, PA) - Researchers at the University of Pennsylvania School of Medicine have determined the structure of an important smallpox virus enzyme and how it binds to DNA. The enzyme, called a topoisomerase, is an important drug target for coming up with new ways to fight smallpox. The researchers present their findings in the August 4 issue of Molecular Cell.

“This enzyme is one of the most closely studied DNA-modifying enzymes in biology,” says Frederic D. Bushman, PhD, Professor of Microbiology, one of the senior authors. “The structure of the DNA complex has been long-awaited.” DNA-modifying enzymes bind to specific sequences in the genetic code to aid in the many steps of DNA replication.


For the full article:

http://www.uphs.upenn.edu/news.....lpxenz.htm
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adedios
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PostPosted: Thu Sep 28, 2006 6:37 pm    Post subject: Studying Membranes at the Nanoscale Reply with quote

Studying Membranes at the Nanoscale
September 28, 2006
UC Davis


The composition of lipid membranes, similar to those that surround living cells, can now be mapped at the nanometer scale. The work, by researchers at Stanford University, the Lawrence Livermore National Laboratory and UC Davis, is published in the Sept. 29 issue of the journal Science.

All living cells are wrapped in a double-layered membrane of fatty lipid molecules. Components of the membrane can move sideways and organize into patches or other structures. This organization can affect, for example, important cell functions and vulnerability to viruses.

But it is very difficult to study these structures because they are so small, measured in tens of nanometers, said Marjorie Longo, professor of chemical engineering and materials science at UC Davis. A nanometer is a billionth of a meter, or about a thirty-millionth of an inch. Scientists want to address questions such as how dynamic or active the membrane is and how small the lipid patches are, she said. An atomic force microscope, which uses a fine needle to probe surfaces, can give a contour map of the surface but without chemical information.

The research group, led by Steven Boxer of Stanford University, used a highly focused beam of charged particles to scan the surface of artificial lipid membranes containing lipid patches developed in Longo's lab. Components of the membrane were previously labeled with heavy isotopes of carbon and nitrogen, mounted on silicon wafers and flash-freeze-dried to preserve structure.

Fragments blasted away by the beam were caught and analyzed, reconstructing the chemical composition of the surface. The process is called Secondary Ion Mass Spectrometry or SIMS. The NanoSIMS instrument, located at the Livermore lab, is one of a handful of its kind in the world, Longo said.

A comparison of AFM and NanoSIMS on the same sample showed that both methods saw the same structures, and NanoSIMS yielded extra information about chemical composition.

Ultimately, the researchers aim to look at actual cell membranes. The work grew out of collaborations between Stanford, Livermore and UC Davis through the Center for Polymer Interfaces and Macromolecular Assemblies, and was funded by the National Science Foundation, National Institutes of Health and the U.S. Department of Energy.
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adedios
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PostPosted: Sat Feb 03, 2007 9:01 am    Post subject: Lipid plays big role in embryonic development Reply with quote

Lipid plays big role in embryonic development
Toni Baker
Feb. 2, 2007

A little-known lipid plays a big role in helping us grow from a hollow sphere of stem cells into human beings, researchers have found.

They found that in the first few days of life, ceramide helps stem cells line up to form the primitive ectoderm from which embryonic tissues develop, says Dr. Erhard Bieberich, biochemist at the Medical College of Georgia.

For the full article:

http://www.mcg.edu/news/2007Ne.....20207.html
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adedios
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Posts: 5060
Location: Angel C. de Dios

PostPosted: Wed Mar 07, 2007 7:46 am    Post subject: Omega-3s boost grey matter, findings may explain why omega-3 Reply with quote

University of Pittsburgh Schools of the Health Sciences
7 March 2007

Omega-3s boost grey matter, findings may explain why omega-3s seem to improve mood

BUDAPEST, HUNGARY, March 7 – Omega-3 fatty acids, found in fatty fish like salmon, are associated with increased grey matter volume in areas of the brain commonly linked to mood and behavior according to a University of Pittsburgh study.

Findings will be presented today by Sarah M. Conklin, Ph.D., postdoctoral scholar at the Cardiovascular Behavioral Medicine Program in the department of psychiatry at the University of Pittsburgh, at the American Psychosomatic Society’s Annual Meeting, held in Budapest, Hungary.

Animal research has shown that raising omega-3 intake leads to structural brain changes. In a separate study presented by Dr. Conklin at the society’s meeting last year, Pitt researchers reported that people who had lower blood levels of omega-3 fatty acids were more likely to have a negative outlook and be more impulsive. Conversely, those with higher blood levels of omega-3s were found to be more agreeable and less likely to report mild or moderate symptoms of depression. In the study being presented today, the researchers sought to investigate if grey matter volume was proportionally related to long-chain omega-3 intake in humans, especially in areas of the brain related to mood, helping them attempt to explain the mechanisms behind the improvement in mood often associated with long-chain omega-3 intake.

Researchers interviewed 55 healthy adult participants to determine their average intake of long-chain omega-3 fatty acids. Grey matter volume was evaluated using high-resolution structural MRI. The researchers discovered that participants who had high levels of long-chain omega-3 fatty acid intake had higher volumes of grey matter in areas of the brain associated with emotional arousal and regulation – the bilateral anterior cingulate cortex, the right amygdala and the right hippocampus.

While this finding suggests that omega-3s may promote structural improvement in areas of the brain related to mood and emotion regulation – the same areas where grey matter is reduced in people who have mood disorders such as major depressive disorder – investigators note that more research is needed to determine whether fish consumption actually causes changes in the brain.
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PostPosted: Wed Sep 26, 2007 1:42 pm    Post subject: New molecular clock from LLNL and CDC indicates smallpox evo Reply with quote

DOE/Lawrence Livermore National Laboratory
26 September 2007

New molecular clock from LLNL and CDC indicates smallpox evolved earlier than believed

Smallpox is older than thought, according to results of a new technique reported in the Sept. 24 issue of the Proceedings of the National Academy of Sciences by researchers from Lawrence Livermore National Laboratory and the Centers for Disease Control (CDC).

The researchers created a molecular clock by looking at the rate of random mutations in the smallpox-causing virus collected in 47 locations around the world, from 1946 – 1977. The variation between the strains was compared to sequences from the most similar animal poxes.

The results indicated that a mild and more severe strain diverged either 16,000 or 68,000 years before present, depending on whether accounts from East Asia or Africa are used to calibrate the molecular clock. In either case, this divergence stretches further back in time than previously believed.

The authors compare hypotheses about where and when strains of the virus evolved. No one hypotheses is ruled out, but an ancient origin seems most plausible since the slowly evolving virus now exclusively infects humans, implying that any intermediate link to an animal host has long since died out.

Collaboration between LLNL’s Pathogen Bioinformatics group and the CDC’s Sequencing and Poxvirus groups took place under a Memorandum of Understanding between the Laboratory and the CDC initiated in early 2003.

The initial research focused on determining viral signatures by looking at unique genetic characteristics. The CDC had recently sequenced the genomes of the various smallpox strains, based on the repository it holds for the World Health Organization (the world’s only other declared smallpox storehouse is in Russia).

The disease was considered eradicated in 1980, three years after the last naturally occurring case in 1977. Vaccinations had been stopped in 1972, following an intensive worldwide effort to wipe out the virus. Smallpox, in its most severe form, was deadly in up to 30 percent of cases.

The researchers said the correlation of historical record and a molecular clock provides a framework that could be applied to studying the natural history of other diseases. Although no particular hypotheses of its evolution is supported or disproved, said corresponding author Inger Damon, M.D., Ph.D., acting chief of the CDC’s Poxvirus and Rabies Branch. “It shows the delineation of tantalizing potential connections between different isolates.”

Analysis of isolates from geographically dispersed areas indicated that local pools of old, and perhaps ancient, strains existed. The human disease may have originated from a rodent-borne virus in Africa. The evolutionary analysis suggests that smallpox disease slowly spread westward from East Asia, which would agree with the oldest smallpox-like descriptions from ancient China as far back as 1122 BC. It is unclear when it first reached the New World – some evidence suggests an ancestral virus arrived with early humans and diversified into a mild version there.

The slow spread out of Asia could explain why smallpox descriptions are missing from ancient Greece or Rome as well as the Old and New Testaments.

The Laboratory’s Shea Gardner and CDC’s Yu Li devised a way to concentrate point mutations in the viral DNA, single nucleotide polymorphisms, or “SNPs.” Four nucleotide bases, arranged in varying sequences, spell out the hereditary information encoded in DNA, the genetic material.

As cells multiply and divide, occasional errors creep in to new copies of the genetic instructions. Some errors are more critical than others. The variation allows some individuals among the offspring to be better-adapted to changing conditions, providing an evolutionary advantage that is passed down to their progeny. Over time, some lines flourish and others die out.

For a reliable molecular clock, it would be nice to see the steady rate of mutation in a general sense without a marked effect of change, pro or con, in any particular gene or subset. So the researchers created a simplified approach for looking across the nearly 200,000 DNA base pairs of the virus genome. They concentrated the mutations for comparing sequences by excerpting stretches in which a single change at one point was flanked by seven unchanged bases at each side.

“We assumed there was a molecular clock ticking,” Gardner said. “The question was what was the rate?”

The Laboratory’s intensive computing capabilities complemented the CDC contribution of calibrating the information with historical accounts, Li said.

“It was a valuable opportunity to be able to compare the genomes,” added Lab scientist Beth Vitalis, who helped analyze the data. She added that additional, related studies of virulence factors are in process.


###
Founded in 1952, Lawrence Livermore National Laboratory has a mission to ensure national security and to apply science and technology to the important issues of our time. Lawrence Livermore National Laboratory is managed by the University of California for the U.S. Department of Energy’s National Nuclear Security Administration.

Laboratory news releases and photos are also available at http://www.llnl.gov/PAO and on UC Newswire.
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