Archive for June 23rd, 2012

Corrupted Proteins Spread Disease | The Scientist

23 June, 2012

See on Scoop.itVirology News

“Many neurological diseases are caused by misfolded proteins that gather in large, destructive clumps, causing neuronal degeneration. Some of these proteins can also convert normal versions into their own twisted images, thus spreading the disease throughout the brain. The classic examples are prion diseases like mad cow disease and Creutzfeld-Jacob disease (CJD). They are caused by misshapen forms of the PrP protein, which corrupts the shapes of normal PrP.

Now, new research published today in the Proceedings of the National Academy of Sciences suggests that Alzheimer’s disease might work in a similar way. Its hallmarks include tangled clumps of amyloid-beta, a peptide (protein fragment) that aggregates in large plaques, which according to the new study, can seed more protein clusters, creating a wave of plaques that spreads through the brain.”

 

Interesting!  As a non-specialist, I have long been struck by the apparent similarities between prion diseases and Alzheimer’s – and now it has been shown that they really are similar in causation.

I just wonder how much of my brain is affected….

See on the-scientist.com

Five Mutations Make H5N1 Airborne | The Scientist

23 June, 2012

See on Scoop.itVirology News

“After more than 6 months of heated discussion, the second group that succeeded in making the H5N1 avian flu transmissible between ferrets, considered a good model for human transmission, has published its results. The paper, which came out today (June 21) in Science, demonstrates that only five mutations are needed to confer this aerosol transmissibility among mammals, and that re-assortment between different types of viruses—a technique used by the other group, which published its results last month in Nature—is not necessary.

Said Fouchier in a press conference “We both find … loss of glycosylation at the tip of the HA molecule, and this loss of glycosylation seems to increase the receptor binding specificity of the HA”. And though not all the mutations identified in the two studies match, “the mutations that are not identical still have a similar phenotypic trait,” he added.”

 

So this is what all the fuss was about?  This is what the NSABB did not want everyone to know?  How could they POSSIBLY think that the international virology and infectious disease community should be kept in the dark about this?  What this work has done has pointed the way along a path that will lead us to understand why and how influenza viruses change in order to more effectively get transmitted when they switch hosts – which is a good thing, surely.

And yet all they see is bioterrorism.

See on the-scientist.com

Avian flu viruses which are transmissible between humans could evolve in nature

23 June, 2012

See on Scoop.itVirology News

It might be possible for human-to-human airborne transmissible avian H5N1 influenza viruses to evolve in nature, new research has found.

The findings, from research led by Professor Derek Smith and Dr Colin Russell at the University of Cambridge, were published June 22 in the journal Science.
Currently, avian H5N1 influenza, also known as bird flu, can be transmitted from birds to humans, but not (or only very rarely) from human to human. However, two recent papers by Herfst, Fouchier and colleagues in Science and Imai, Kawaoka and colleagues in Nature reveal that potentially with as few as five mutations (amino acid substitutions), or four mutations plus reassortment, avian H5N1 can become airborne transmissible between mammals, and thus potentially among humans. However, until now, it was not known whether these mutations might evolve in nature.
The Cambridge researchers first analysed all of the surveillance data available on avian H5N1 influenza viruses from the last 15 years, focusing on birds and humans. They discovered that two of the five mutations seen in the experimental viruses (from the Fouchier and Kawaoka labs) had occurred in numerous existing avian flu strains. Additionally, they found that a number of the viruses had both of the mutations.
Colin Russell, Royal Society University Research Fellow at the University of Cambridge, said: “Viruses that have two of these mutations are already common in birds, meaning that there are viruses that might have to acquire only three additional mutations in a human to become airborne transmissible. The next key question is ‘is three a lot, or a little?’ “

 

So: was it a good idea to publish those two papers on mutating H5N1 viruses, or not?  Given that as I and many other more famous people pointed out, if you don’t know what makes the viruses mammal-to-mammal transmissible, you don’t know what to look for – and now we do, and look what they found.  This story will run, and run, and run – so we really, really should include an H5 consensus HA in seasonal flu vaccines!!

See on www.sciencedaily.com

Non-canonical translation in RNA viruses

23 June, 2012

See on Scoop.itVirology News

“Viral protein synthesis is completely dependent upon the translational machinery of the host cell. However, many RNA virus transcripts have marked structural differences from cellular mRNAs that preclude canonical translation initiation, such as the absence of a 5′ cap structure or the presence of highly structured 5′UTRs containing replication and/or packaging signals. Furthermore, whilst the great majority of cellular mRNAs are apparently monocistronic, RNA viruses must often express multiple proteins from their mRNAs. In addition, RNA viruses have very compact genomes and are under intense selective pressure to optimize usage of the available sequence space. Together, these features have driven the evolution of a plethora of non-canonical translational mechanisms in RNA viruses that help them to meet these challenges. Here, we review the mechanisms utilized by RNA viruses of eukaryotes, focusing on internal ribosome entry, leaky scanning, non-AUG initiation, ribosome shunting, reinitiation, ribosomal frameshifting and stop-codon readthrough. The review will highlight recently discovered examples of unusual translational strategies, besides revisiting some classical cases.”

 

Great article for anyone interested in how RNA viruses subvert cellular processes.

See on vir.sgmjournals.org

Condoms not effective against HPV or herpes

23 June, 2012

See on Scoop.itVirology News

“Viral STDs make up the modern “4-H club.” Herpes simplex virus (HSV), human papilloma virus (HPV), hepatitis (B and C), and HIV are the most common STDs, causing pain, cancer, liver disease and AIDS, respectively.

Condoms significantly decrease transmission rates of the most life-threatening viruses, HIV and hep B and C.

Unfortunately, condoms do not do an adequate job of protecting against human papilloma or herpes simplex virus infections. Women diagnosed with HPV are often mystified and frustrated, having been “super careful,” or picky, in choosing intimate partners and faithfully using condoms for all intercourse.

But UCSF researchers have shown these viruses to be present on genital skin with no symptoms that might prompt diagnosis and treatment. That means HPV and HSV can be deposited on the condom’s outer surface from viral particles living on the scrotum, penile shaft not covered by the condom or vaginal/vulvar tissues.”

 

Interesting – because it’s been known a while that condoms are less effective in preventing spread of HPV than for bacterial STDs and HIV, and now we know why.  The only things that can really prevent the transmission of these agents, in the absence of abstinence, is vaccination.

See on www.sfgate.com

[dsRNA] Treatment for deadly bee virus promising

23 June, 2012

See on Scoop.itVirology News

“There’s buzz about a new treatment that could save bee populations from a deadly virus.
Researchers at the University of Manitoba have found a way to suppress the deformed-wing virus (DWV), which has had catastrophic effects on bee colonies worldwide, causing many to have crumpled or deformed wings.
Entomology PhD student Suresh Desai fed his bees double-stranded RNA, a treatment that prevented the virus from expressing itself in the host.
“It gives us a little bit of hope that we can manage this virus, because there is no control mechanism right now,” he said.
The study, published online on Insect Molecular Biology on June 12, showed bees fed the double-stranded RNA in a syrup and then inoculated with the virus had a much better survival rate than those who weren’t. RNA is much like DNA, but is in a single strand. It carries the genetic material of some viruses, including DWV. RNA is taken from the DWV and then converted into a double strand. When introduced in the bee, it suppresses the viral RNA.”

 

I find it fascinating that the dsRNA that we as plant virologists grew to know and love in the 1980s – because it’s easier to isolate from plants than ssRNA, and far more stable – has newly become so much more useful as an anti-viral therapeutic.  And you can isolate a tonne of dsRNA from virus-infected insects, too, so it’s also interesting why exogenous material should be effective.

See on www.winnipegfreepress.com

The subgenomic promoter of brome mosaic virus folds into a stem–loop structure capped by a pseudo-triloop that is structurally similar to the triloop of the genomic promoter

23 June, 2012

See on Scoop.itVirology News

In brome mosaic virus, both the replication of the genomic (+)-RNA strands and the transcription of the subgenomic RNA are carried out by the viral replicase. The production of (−)-RNA strands is dependent on the formation of an AUA triloop in the stem–loop C (SLC) hairpin in the 3′-untranslated region of the (+)-RNA strands. Two alternate hypotheses have been put forward for the mechanism of subgenomic RNA transcription. One posits that transcription commences by recognition of at least four key nucleotides in the subgenomic promoter by the replicase. The other posits that subgenomic transcription starts by binding of the replicase to a hairpin formed by the subgenomic promoter that resembles the minus strand promoter hairpin SLC. In this study, we have determined the three-dimensional structure of the subgenomic promoter hairpin using NMR spectroscopy. The data show that the hairpin is stable at 30°C and that it forms a pseudo-triloop structure with a transloop base pair and a nucleotide completely excluded from the helix. The transloop base pair is capped by an AUA triloop that possesses an extremely well packed structure very similar to that of the AUA triloop of SLC, including the formation of a so-called clamped-adenine motif. The similarities of the NMR structures of the hairpins required for genomic RNA and subgenomic RNA synthesis show that the replicase recognizes structure rather than sequence-specific motifs in both promoters.

See on rnajournal.cshlp.org