MicrobiologyBytes

With the fall in H1N1 “swine flu” influenza cases recently, it has become fashionable for the media to run “What was all the fuss about” stories on the same page as “OMG, it’s going to be bad” stories. The problem with influenza is that it is one of the most unpredictable of all viruses, and while an upsurge in the number of cases can be expected as the winter flu season gets going in the northern hemisphere, the real concern is that this new pandemic virus might “turn nasty” in the second wave, just as in 1918 a much more pathogenic variant of that virus followed the relatively benign first wave of cases.

There are two ways in which this could happen. The first is that the present virus acquires spontaneous mutations which make it more pathogenic. The other possibility is that the virus recombines with a highly pathogenic influenza virus though the process known as reassortment – swapping of genes when two different strains infect the same cell. And there’s a good candidate for that out there – the highly pathogenic H5N1 avian influenza virus. Unlike H1N1, H5N1 has a hard time infecting humans, so it’s unlikely that these viruses would meet. But if they did…

The good news comes from Egypt, where H5N1 is relatively common, and a (worrying) case of H5N1/H1N1 co-infection was recently reported. The Ministry of Health has now discounted the rumour of a co-infection with the two viruses. In addition, a University of Maryland/NIH study suggests that co-infections of H1N1 with seasonal flu viruses do not produce chimeric or reassortant viruses. The H1N1 strain seems to outcompete seasonal viruses, possibly demonstrating this pandemic strain is not under biological pressure and is perhaps more efficiently communicable. Certainly, the past pattern seems to suggest that H1N1 pandemic seem to suppress outbreaks of other strains for some time.

A phase I clinical trial conducted by scientists from the University of Leicester tested 100 healthy volunteers with an H1N1 vaccine to see how their immune system responded. Trial leader Dr Iain Stephenson found 80 per cent of the volunteers showed a “strong, potentially protective” response after one dose, with more than 90 per cent showing the same response after two doses. The results suggest that one vaccine dose may be sufficient to protect against A(H1N1) swine flu, rather than two. Larger trials are now under way around the world involving up to more than 6,000 adults and children.

Reasons to be cheeful.

Related:

• H5N1 and 1918 pandemic influenza virus infection and the lungs
• Spotting pandemic influenza viruses
• How influenza pandemics get started
• The Pathogenicity of Pandemic Influenza Viruses
• The Great Flu – a free online game

e-Bug is a new online learning tool made up of educational activities for primary and secondary school-age children, complemented by online games, on microbes, hygiene, antibiotic use and vaccines. The programme features age-appropriate animated characters and cartoon microbes; and lesson plans and materials for teachers. Topics include hygiene measures to stop the spread of swine flu and other respiratory infections. The programme also educates children – our future generation of antibiotic users – on the importance of the prudent use of antibiotics. Antibiotics are currently the most common medicines given to children, and increased antibiotic use is linked to increased resistance.

e-Bug is being launched in ten EU countries with some of the highest antibiotic use and largest populations, making up 55% of the EU population. The 10 countries which will be implementing e-Bug are Belgium, Czech Republic, Denmark, England, France, Greece, Italy, Poland, Portugal and Spain. The eight countries which are seeking funding to implement it are Croatia, Lithuania, Latvia, Finland, Hungary, Ireland, Slovenia and Slovakia. The site will not be formally included in the English school curriculum but an information pack will be sent to all schools as a hard copy resource for teachers.

Related:

• The Great Flu – a free online game
• Sneeze

via Wired

Retrotransposons present a threat to genome stability as a result of their dispersed nature, with 32 copies of the Ty1 element per haploid yeast genome. Ty1 retrotransposons replicate through an RNA intermediate that is reverse-transcribed following encapsidation into a retrovirus-like particle, and then integrated into the host cell genome. These integrated Ty1 copies provide two challenges to genome stability: when Ty1 repeats are present as inverted pairs, they function to stall replication forks; and when recombination machinery is subsequently recruited to these stalled forks, the dispersed Ty1 elements provide numerous templates for ectopic repair. Abundant evidence exists for the association of Ty1 sequences with chromosomal translocations that may result from ectopic recombination in industrial, laboratory, and evolutionary settings. Most notably, strains evolved under nutrient limitation contained chromosomal translocation breakpoints largely coincident with Ty1 elements.

A recent paper describes a set of yeast strains with Ty1 copy numbers as many as 10 times that of the WT strain. This increased Ty1 content not only promotes genome instability, but further enables the identification of genes and pathways that contribute to the suppression of retrotransposon-mediated instability. The paper shows that increasing retrotransposon abundance is detrimental to the fitness and stability of the yeast genome, even in the absence of ongoing retrotransposition. The ability of higher eukaryotic cells to maintain levels of repetitive DNA at much higher levels than in yeast cells underscores the importance of highly efficient and precisely controlled DNA replication and error prevention machinery to safeguard against the deleterious potential of such expansion. Yet the persistence of retrotransposon DNA, despite the inherent risk posed by its maintenance, suggests that the resulting genome alterations confer an important and ongoing underlying evolutionary benefit to cells, driving adaptation and evolution of the genome.

Retrotransposon overdose and genome integrity. PNAS USA August 4, 2009. doi: 10.1073/pnas.0906552106
Yeast and mammalian genomes are replete with nearly identical copies of long dispersed repeats in the form of retrotransposons. Mechanisms clearly exist to maintain genome structure in the face of potential rearrangement between the dispersed repeats, but the nature of this machinery is poorly understood. Here we describe a series of distinct “retrotransposon overdose” (RO) lineages in which the number of Ty1 elements in the Saccharomyces cerevisiae genome has been increased by as much as 10 fold. Although these RO strains are remarkably normal in growth rate, they demonstrate an intrinsic supersensitivity to DNA-damaging agents. We describe the identification of mutants in the DNA replication pathway that enhance this RO-specific DNA damage supersensitivity by promoting ectopic recombination between Ty1 elements. Abrogation of normal DNA replication leads to rampant genome instability primarily in the form of chromosomal aberrations and confirms the central role of DNA replication accuracy in the stabilization of repetitive DNA.

Related:

• Phoenix from the ashes: The 5 million year old virus
• T Cell Responses to Human Endogenous Retroviruses in HIV-1 Infection

Neglected tropical diseases (NTDs) are the most common conditions affecting the poorest 500 million people living in sub-Saharan Africa (SSA), and together produce a burden of disease that may be equivalent to up to one-half of SSA’s malaria disease burden and more than double that caused by tuberculosis. Approximately 85% of the NTD disease burden results from helminth infections. Hookworm infection occurs in almost half of SSA’s poorest people, including 40–50 million school-aged children and 7 million pregnant women in whom it is a leading cause of anaemia. Schistosomiasis is the second most prevalent NTD after hookworm (192 million cases), accounting for 93% of the world’s number of cases and possibly associated with increased horizontal transmission of HIV/AIDS. Lymphatic filariasis (46–51 million cases) and onchocerciasis (37 million cases) are also widespread in SSA, each disease representing a significant cause of disability and reduction in the region’s agricultural productivity. There is a dearth of information on Africa’s non-helminth NTDs. The protozoan infections, human African trypanosomiasis and visceral leishmaniasis, affect almost 100,000 people, primarily in areas of conflict in SSA where they cause high mortality, and where trachoma is the most prevalent bacterial NTD (30 million cases). However, there are little or no data on some very important protozoan infections, e.g., amebiasis and toxoplasmosis; bacterial infections, e.g. typhoid fever and non-typhoidal salmonellosis, the tick-borne bacterial zoonoses, and non-tuberculosis mycobaterial infections; and arboviral infections. Thus, the overall burden of Africa’s NTDs may be severely underestimated. A full assessment is an important step for disease control priorities, particularly in Nigeria and the Democratic Republic of Congo, where the greatest number of NTDs may occur.

If you want to make a difference, start here.

Neglected Tropical Diseases in Sub-Saharan Africa: Review of Their Prevalence, Distribution, and Disease Burden. 2009 PLoS Negl Trop Dis 3(8): e412. doi:10.1371/journal.pntd.0000412

Related:

• Schistosomiasis control in Mali – or not
• 7 million pregnant women in sub-Saharan Africa infected with hookworm
• Parasitic worm may increase susceptibility to AIDS virus
• Neglected Tropical Diseases in Latin America and the Caribbean