Archive for May, 2008

PIPO, I see you…

30 May, 2008

Now here’s an interesting thing: a completely unsuspected gene – as in, on open reading frame (ORF) that actually DOES something – in one of the best-studied familes of plant viruses.  From the International Service for the Acquisition of Agribiotech Applications (ISAAA)’s CropBiotech Update 30 May 2008:

Scientists Discover Hidden Gene in Major Plant Virus Family

The virus family Potyviridae includes more than 30 percent of known plant virus species, most of which are of great agricultural significance such as the potato virus Y, turnip mosaic virus and wheat streak mosaic virus. Scientists from the Iowa State University, working with colleagues from the University College Cork in Ireland, have discovered a tiny gene present in all members of this virus family. Without this gene, the viruses are harmless.

Using a gene-finding software, the team identified a stretch of nucleotide bases that overlaps with a much larger and well characterized gene in potyviruses. They called the new gene pipo (short for pretty interesting potyvirus ORF). Alterations in the sequence of the pipo gene, while leaving the polyprotein amino acid sequence unaltered, were found to be lethal for the viruses.

The team led by Allen Miller and John Atkins are now working to determine the function of gene during infection as well as how the pipo protein is expressed from the viral genome. For this, the U.S. Department of Agriculture National Research Initiative (USDA-NRI) has awarded them with a $400,000 competitive grant.

For more information, visit \http://www.public.iastate.edu/~nscentral/ Read the paper published by PNAS at http://www.pnas.org/cgi/reprint/105/15/5897

Nice one, guys…$400 000 should buy a few more ORFs…B-)  Seriously, though, the dogma has been for years that potyviruses, like picornaviruses, have a single long (~10kb) ORF, which expresses a polypeptide from the genomic RNA which is cotranslationally processed into a number of different proteins – and that was all there was.  This discovery is like finding a new and secret drawer in an old and familiar chest of drawers, or an extra pocket in your trousers.  Or, as I did recently, that there wer two interior lights in my car which I had not known of for six years…but I digress.

In the words of the authors:

“We report the discovery of a short ORF embedded within the P3 cistron of the polyprotein but translated in the +2 reading-frame. The ORF, termed pipo, is conserved and has a strong bioinformatic coding signature throughout the large and diverse Potyviridae family. Mutations that knock out expression of the PIPO protein in Turnip mosaic potyvirus but leave the polyprotein amino acid sequence unaltered are lethal to the virus. Immunoblotting with antisera raised against two nonoverlapping 14-aa antigens, derived from the PIPO amino acid sequence, reveals the expression of an ~25-kDa PIPO fusion product in planta. This is consistent with expression of PIPO as a P3-PIPO fusion product via ribosomal frameshifting or transcriptional slippage at a highly conserved G1-2A6-7 motif at the 5′ end of pipo. This discovery suggests that other short overlapping genes may remain hidden even in well studied virus genomes (as well as cellular organisms)…”

They go on to tout the virtues of the “software package MLOGD”, which it turns out is from here (Firth AE, Brown CM (2006) Detecting overlapping coding sequences in virus genomes. BMC Bioinformatics 7:75), and is the Maximum Likelihood Overlapping Gene Detector.   They say:

“Tests show that, from an alignment with just 20 mutations, MLOGD can discriminate non-overlapping CDSs from non-coding ORFs with a typical accuracy of up to 98%, and can detect CDSs overlapping known CDSs with a typical accuracy of 90%. In addition, the software produces a variety of statistics and graphics, useful for analysing an input multiple sequence alignment.”

And yes, it does make nice pictures: see this and this for examples.

All of which simply goes to reinforce my conviction that virus genomes may be generally quite small, but small does not necessarily mean simple.  Small means having to compress information, reuse sequences – and overlap ORFs in unsuspected ways.

Bird Flu Vaccine Launched – But For Whom?

22 May, 2008

The online 20 May issue of Nature News trumpets the release and marketing of a new H5N1 bird flu vaccine: GlaxoSmithKline’s Prepandrix has just been approved by the European Commission. 

Published online 20 May 2008 | Nature | doi:10.1038/news.2008.844

Bird flu vaccine to hit the shelves

Europe approves pandemic vaccine; countries must decide own strategies.

Tony Scully

The European Commission has approved a new vaccine against the H5N1 bird flu virus — the first vaccine designed to ward off a future pandemic. But how the drug, called Prepandrix, will be deployed by national governments remains unclear.The vaccine, produced by the UK drug giant GlaxoSmithKline, is aimed at the H5N1 strain currently circulating in birds as epidemiologists think that this is the most likely strain to cause a human pandemic. H5N1, which originated in south-east Asia and is carried by migrating birds and domestic poultry, has caused 382 human cases and 241 deaths worldwide since 2003.

Prepandrix targets an antigen from an H5N1 strain called A/Vietnam/1194/04, which has been detected in birds in Asia, Europe and Africa. Clinical tests have shown that the vaccine is also effective against other closely related variants of H5N1, such as H5N2. The release of the vaccine is seen as a gamble that any future pandemic strain will closely resemble the Vietnamese version used to derive the vaccine.

The article goes on to describe how “The first orders for Prepandrix were placed last year by Finland and Switzerland, before it had been approved by the European Commission. In 2007, sales for Prepandrix totalled US$284 million worldwide….”

Yes.  Well.  Um.  Where is the pandemic going to hit first?  Finland?  Switzerland?  I doubt it.  How about Indonesia, Thailand, Vietnam, Turkey, Egypt…or, horror of horrors, India or China?  All the places which will need a LOT of doses, cheap.

Do they stand any chance of getting them?  Not unless they have preordered.  And not – in the case a pandemic strikes – unless they are willing to take military action to prise their stocks out of the hands of the governments in the developed countries where the vaccines are made.

A senior WHO official stated the case very succinctly, at the Virus Africa virology conference in Cape Town in November 2005: “You people in the developing countries will be on your own if the pandemic comes.  You need to make your own vaccine…”.

We wait in hope.

Painting With Viruses

21 May, 2008

Suhail Rafudeen should be a virologist…B-)  Here’s another piece of treasure from his Web trawling:

Public release date: 20-May-2008

Federation of American Societies for Experimental Biology

Scientists ‘paint’ viruses to track their fate in the body New study in the FASEB Journal describes a molecular ‘painting’ method to colors the culprit

Bethesda, MD-Biologists from Austria and Singapore developed a technique that adds a new twist on the relationship between biology and art. In an article recently published online in The FASEB Journal (http://www.fasebj.org) and scheduled for the August 2008 print issue, these researchers describe how they were able to coat-or paint-viruses with proteins. This breakthrough should give a much-needed boost to the efficiency of some forms of gene therapy, help track and treat viral disease and evolution, improve the efficiency of vaccines, and ultimately allow health care professionals track the movement of viral infections within the body. Specifically, the new method should make it easier to track and treat infectious diseases such as HIV/AIDS, influenza, hepatitis C, and dengue fever. And because viruses can also be used to introduce biotechnology drugs and replacement genes, and act as vaccines, this research should lead to new treatments for cancer, cardiovascular, metabolic and inherited disorders.

“This technology should provide a new tool for the treatment of many diseases,” said Brian Salmons, one of scientists who co-authored the study. “Even if you are working with a virus that is unknown or poorly characterized, it is still possible to modify or paint it. This is very interesting for emerging diseases.”

In the article, Salmons and colleagues explain how they mixed purified proteins (glycosylphophatidylinositol anchor proteins) with lipid membranes to make it possible to bind these proteins to the outer “skin” (the lipid envelope) of viruses. Even with the new paint job, the viruses remained infectious. While the experiment only involved one type of protein and two types of viral vectors, Salmons says the technique could be expanded and used to apply “paint” made up of other proteins, dyes, and a variety of unique markers.

“Biology and art converge daily: people paint their nails, color their hair, and tattoo their skin,” said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal. “Now this convergence has entered a new dimension as painted viruses permit scientists to track, cure and prevent disease.”

I think Dr Weissman may have an exciting life outside of science…B-)  But seriously, this is a VERY useful development: keeping viruses infectious while being able to track them, even in real time, and show where different viruses infecting the same cells end up…the possibilities expand as you think of them.

Truly little nanomachines, viruses: and now you can specify the colour.

What Rough Beast

19 May, 2008

I was surprised and rather gratified to see – via a suitably modest no-commentary post in MicrobiologyBytes - that ViroBlogy has been noticed by none other than the June editorial of Nature Reviews Microbiology.

Along with rather more material on MicrobiologyBytes and Small Things Considered.  But hey, a review’s a review…!

There are a number of useful comments and other links in the blog version of the post, on how to actually interact with such material, and the potential of “Web 2.0″ applications.

So get busy, students…the wiki is coming – in fact, it was already established, but will be re-invented before the second semester – and your participation is vital.


Follow

Get every new post delivered to your Inbox.

Join 594 other followers