Virology News

"Introduction
The publication in this issue of these research papers on the airborne tranimssion [sic] of H5N1 marks the end of 8 months of controversy over whether some of the data, now freely accessible, should be withheld in the public interest."

I think this is an important landmark in the so-called "dual use" debate: that is, the propensity of bodies in the US to attempt to regulate the release of information that MAY be usable in the making of bioweapons, or be usable in bioterror attacks.

Let us diffidently point out at this juncture that it is only really the superpowers who are definitively known in recent years to have had bioweapons programmes - apart from apartheid-era South Africa, that is! - and that damn nearly ANYTHING published on transmission or mechanisms of pathogenicity of human or animal pathogens (or even plant, for that matter) could be termed "dual use" if someone wanted to - and censored as a result.

It is also - as I tire of pointing out - possible to PROTECT against H5NX viruses using conventional vaccines right now - and the new universal flu vaccines coming on stream will almost certainly make this even more feasible.

The fact is that H5N1 flu is an ever-present threat to people living in Egypt, Indonesia, Cambodia, Viet Nam, Thailand and China - WITHOUT being weaponised.  It is no more than a notional threat to the US or Europe - and keeping information that could help in understanding how or how soon the virus could mutate to pandemicity out of people's hands, is simply stupid. 

The 2009 swine fly pandemic may have killed 284,500 people globally, 15 times more people than reported at the time, according to the first report to estimate the death toll.

Which is NO surprise to those of us who know that the death toll from SEASONAL flu is between 250 000 and 400 000 people per year - if you count in all those pesky developing countries.  Most medicos I know are dumbfounded when I tell them this....

"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....

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!!

Couldn't resist this one, and had fun dreaming up all sorts of punchlines.  Like" "They're both annoying, they both hurt, and they make you drool".  Sorry...!

It's actually a sales pitch for a salivary HPV test, but the virology underlying it is interesting: oral sex can lead to oral HPV infection with high-risk types that are associated with oral cancers.  However, in the absence of oral sex you can also get high-risk types in the oral area, and antibodies to the viruses can be detected in saliva without any oral infection.

Vaccination against hepatitis B seems to protect against the virus for 25 years, suggesting that booster shots are unnecessary, according to a study from Taiwan that covered several thousand people.  “Universal vaccination in infancy provides long-term protection,” wrote lead author Yen-Hsuan Ni, from the National Taiwan University in Taipei.

Good news indeed - because chronic infection with HBV, which occurs more often if you get it as a child, leads to a far higher incidence of liver cancer and a lifelong carrier status.  And there's over 300 million people infected, so it's a SERIOUS problem.

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.

BMV!! I worked on bromoviruses in general and BMV in particular from 1977 to around 1985, and collected every paper on them - and especially the mol biol. It was always obvious, once the sequences were known, that origins of replication and the subgenomic promoter were not sequence-delimited - and now we see that it's a structure. Cool stuff!!

South Africa recently claimed a victory. In May, it won the right to host the world’s biggest radio telescope.  The $2 billion project, said Derek Hanekom, Deputy Minister of Science and Technology at BIO’s ‘The BRICS and Beyond’ special session (June 18) sent out a sign that the country has left behind its troubled past and is ready for business. Beyond astronomy, and its azure skies, South Africa is a market poised for growth and a gateway to the rest of the continent. Over the last 20 years, the government has embraced “innovative thinking,” said Hanekom. While addressing poverty issues, and providing help for the 5.6 million people who are HIV positive, the state has come up with game plan to spur the economy. South Africa, as most other BRIC countries have done before, is embracing the idea of a Bioeconomy as an engine for growth. The state sees potential in genetically modified crops for pest and drought resistance and grasses as cellulosic material for second-generation biofuels. Exploiting algae is also high on the agenda, in the short term, as a source of protein for animal feed, and in the long term as a biofuel.

Ja.  Really??  Why is it so damn hard to get money, then??

The health of the honeybee and, indirectly, global crop production are threatened by several biotic and abiotic factors, which play a poorly defined role in the induction of widespread colony losses. Recent descriptive studies suggest that colony losses are often related to the interaction between pathogens and other stress factors, including parasites. Through an integrated analysis of the population and molecular changes associated with the collapse of honeybee colonies infested by the parasitic mite Varroa destructor, we show that this parasite can de-stabilise the within-host dynamics of Deformed wing virus (DWV), transforming a cryptic and vertically transmitted virus into a rapidly replicating killer, which attains lethal levels late in the season. The de-stabilisation of DWV infection is associated with an immunosuppression syndrome, characterized by a strong down-regulation of the transcription factor NF-κB. The centrality of NF-κB in host responses to a range of environmental challenges suggests that this transcription factor can act as a common currency underlying colony collapse that may be triggered by different causes. Our results offer an integrated account for the multifactorial origin of honeybee losses and a new framework for assessing, and possibly mitigating, the impact of environmental challenges on honeybee health.

Instead of going to great lengths to delay or avoid vaccination, as some American parents do, mothers in the developing world struggle to get to clinics and to get the required vaccinations.

You HAVE to wonder at it...children who were vaccinated, by parents who knew what it was to see people die of polio, diphtheria and measles, not vaccinating THEIR children, "because it's dangerous!"
The pity is that it's not them that will suffer - except at second hand.  Thanks, @dr_agoglesby! 

"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.

"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.

"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.

"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.

At least 10 Zimbabwean members of parliament get circumcised as part of a campaign to reduce HIV and Aids cases.

Might stop 'em having sex for a while, which would also help!