Virology News

The oncogenic potential of papillomaviruses (PVs) has been appreciated since the 1930s yet the mechanisms of virally-mediated cellular transformation are still being revealed. Reasons for this include: a) the oncoproteins are multifunctional, b) there is an ever-growing list of cellular interacting proteins, c) more than one cellular protein may bind to a given region of the oncoprotein, and d) there is only limited information on the proteins encoded by the corresponding non-oncogenic PVs. The perspective of this review will be to contrast the activities of the viral E6 and E7 proteins encoded by the oncogenic human PVs (termed high-risk HPVs) to those encoded by their non-oncogenic counterparts (termed low-risk HPVs) in an attempt to sort out viral life cycle-related functions from oncogenic functions. The review will emphasize lessons learned from the cell culture studies of the HPVs causing mucosal/genital tract cancers.

"A classified briefing from U.S. intelligence officials helped persuade a majority of members of a government advisory board that the benefits of publishing two controversial H5N1 avian influenza studies outweighed the risks, according to testimony presented yesterday at a U.S. Senate hearing.

The late March briefing to the National Science Advisory Board for Biosecurity (NSABB) left "the impression that the risk of misuse did not appreciably increase with full publication and there is a high likelihood of undesirable political consequences to not publishing," microbiologist Paul Keim of Northern Arizona University in Flagstaff, acting chair of NSABB, told the Committee on Homeland Security and Governmental Affairs."

"Influenza A virus possesses a segmented genome of eight negative-sense, single-stranded RNAs. The eight segments have been shown to be represented in approximately equal molar ratios in a virus population; however, the exact copy number of each viral RNA segment per individual virus particles has not been determined. We have established an experimental approach based on multicolor single-molecule fluorescent in situ hybridization (FISH) to study the composition of viral RNAs at single-virus particle resolution. Colocalization analysis showed that a high percentage of virus particles package all eight different segments of viral RNAs. To determine the copy number of each RNA segment within individual virus particles, we measured the photobleaching steps of individual virus particles hybridized with fluorescent probes targeting a specific viral RNA. By comparing the photobleaching profiles of probes against the HA RNA segment for the wild-type influenza A/Puerto Rico/8/34 (PR8) and a recombinant PR8 virus carrying two copies of the HA segment, we concluded that only one copy of HA segment is packaged into a wild type virus particle. Our results showed similar photobleaching behaviors for other RNA segments, suggesting that for the majority of the virus particles, only one copy of each RNA segment is packaged into one virus particle. Together, our results support that the packaging of influenza viral genome is a selective process."

Influenza virus cutaway by Russell Kightley Media

Rapid production of influenza vaccine antigen is an important challenge when a new pandemic occurs. Production of recombinant antigens in plants is a quick, cost effective and up scalable new strategy for influenza vaccine production.  In this study, we have characterized a recombinant influenza haemagglutinin antigen (HAC1) that was derived from the 2009 pandemic H1N1 virus and expressed in tobacco plants. Volunteers vaccinated with the 2009 pH1N1 oil-in-water adjuvanted vaccine provided serum and lymphocyte samples that were used to study the immunogenic properties of the HAC1 antigen in vitro. By 7 d post vaccination, the vaccine fulfilled the licensing criteria for antibody responses to the HA detected by haemagglutination inhibition and single radial hemolysis. By ELISA and ELISPOT analysis we showed that HAC1 was recognized by specific serum antibodies and antibody secreting cells, respectively. We conducted a kinetic analysis and found a peak of serum HAC1 spec antibody response between day 14 and 21 post vaccination by ELISA. We also detected elevated production of IL-2 and IFNγ and low frequencies of CD4+ T cells producing single or multiple Th1 cytokines after stimulating PBMCs (peripheral blood mononuclear cells) with the HAC1 antigen in vitro. This indicates that the antigen can interact with T cells, although confirming an effective adjuvant would be required to improve the T-cell stimulation of plant based vaccines. We conclude that the tobacco derived recombinant HAC1 antigen is a promising vaccine candidate recognized by both B- and T cells.

Fraunhofer USA, waving the Green Vaccine flag: way to go....

We've all heard the myths and hypotheses about the origins of the epidemic caused by the HI virus, but a new book, “Tinderbox: How the West Sparked the AIDS Epidemic and How the World Can Finally Overcome It”, sheds more light on where it all began.

I've covered this before, but it's a nice review - complete with spoilers like how Beatrice Hahn and team have shown that a chimpanzee SIV from Cameroon is the closest relative of HIV-1 group M viruses.  The gun doesn't smoke more than that.

"Dr. Millman also helped create a test for hepatitis B that substantially reduced the risk of infection from blood transfusions.

Hepatitis B is one of five viruses known to cause liver inflammation; it can lead to cancer. By some estimates, more than 350 million people are carriers, especially in Asia and Africa. The virus spreads as H.I.V. does — via blood, semen and other bodily fluids — but is more infectious."

The first virus-like particle vaccine - albeit non-recombinant, because it was purified from plasma obtained from infected people.

“The animal actually makes the vaccine inside its body by producing the FMD protein necessary to create an immune response,” Dr. Rodriguez said, according to the BBC. “It’s a very good innovation – the most effective way to date and very promising technology. I think it’s going to revolutionize the way we look at FMD vaccines around the world today.”

So a DNA vaccine, then?  Hardly revolutionary - but ANYTHING that changes the primitive attitude governments have to the use of FMDV vaccines is to be welcomed.

"Bacteria and their viruses (called bacteriophages, or phages), have been found in virtually every ecological niche on Earth. Arid regions, including their most extreme form called deserts, represent the single largest ecosystem type on the Earth's terrestrial surface. The Namib desert is believed to be the oldest (80 million years) desert. We report here an initial analysis of bacteriophages isolated from the Namib desert using a combination of electron microscopy and genomic approaches. The virus-like particles observed by electron microscopy revealed 20 seemingly different phage-like morphologies and sizes belonging to the Myoviridae and Siphoviridae families of tailed phages. Pulsed-field gel electrophoresis revealed a majority of phage genomes of 55-65 kb in length, with genomes of approximately 200, 300, and 350 kb also observable. Sample sequencing of cloned phage DNA fragments revealed that approximately 50% appeared to be of bacterial origin. Of the remaining DNA sequences, approximately 50% displayed no significant match to any sequence in the databases. The majority of the 16S rDNA sequences amplified from DNA extracted from the sand displayed considerable (94-98%) homology to members of the Firmicutes, and in particular to members of the genus Bacillus, though members of the Bacteroidetes, Planctomycetes, Chloroflexi, and delta-Proteobacteria groups were also observed."

This serves as a neat, if slightly dated, little introduction to my latest endeavour - and an account of a field trip this last week into the Namib Desert.

I was fortunate enough some time ago to have been invited by Don Cowan, presently of University of Pretoria, to accompany his team to the Gobabeb Research Station inland of Walvis Bay, in Namibia's Namib Desert. They work on extremophiles, and the Namib is a great environment for mining bugs that can withstand high salt and temperatures and severe desiccation - oh, and photosynthesise underground, hiding under semi-tranlucent quartz rocks embedded in the surface soil. The thinking was that, given my long-time interest in viral diversity and newly-acquired means to do oceanic viromics, I would be interested and even of some help.

And so it has come to pass: I will have my very own hypolith (=rock-colonising blue-green algae) scrapings and the result of diafiltration and concentration of washings of a good few kilos of red dune sand to play with as far as virus genome sequencing and even EM and analytical centrifugation go.

We will have fun in the coming months...that, and we will obviously HAVE to go back to Gobabeb, to further investigate whatever it is we find. A terrible, harsh place, but SOMEONE has to go there...so I'll take the pain. B-)

Phage graphic courtesy of Russell Kightley Media