Thursday, March 17, 2011

Using Magnets to Image Influenza’s M2 Protein: Implications for Drug Design

Researchers from Florida State and BYU recently used a 900 megahertz magnet to image the M2 protein of influenza A. The magnet offers an inside view of the virus similar to the images seen with magnetic resonance imaging (MRI). Because the M2 protein exists in a water-repellent cell membrane, it cannot be imaged using MRI because MRI scans spin hydrogen water molecules. To image M2 researchers used a technique called solid-state nuclear magnetic resonance spectroscopy that spins molecules other than hydrogen and makes it possible to image proteins outside of a watery medium.

By focusing on nitrogen atoms, researchers found that M2 is activated in an acidic environment. Histidine carries protons from the host cell into the virus and tryptophan acts as a gate to let the protons through. Apparently, the passage of protons through M2 eventually allows the virus to reproduce.

Recently, major M2 inhibitors such as Amantadine and Rimantidine have suffered in their effectiveness because of viral mutation (i.e. M2 has changed shape). In 2006, the CDC even recommended against the use of these common drugs. Because this atomic mechanism is novel, researchers hope that it can be used to develop new antivirals against influenza. Its uniqueness makes researchers believe that any drug that utilizes the pathway will be extremely effective for a long time because it appears essential to viral replication.

-Owen Marecic

Wednesday, March 16, 2011

Norovirus vaccine candidate effective in Mice

Scientists at Ohio State University have successfully tested a new vaccine against norovirus in mice. According to the study, the vaccine induced high levels of antibodies, white blood cells, and other parts of the immune response. This particular vaccine is not amplified using cell culture, but is amplified using a vector-based technique similar to the one being tried with HIV and Hepatitis C vaccine trials. This vaccine uses vesicular stomatitis virus (VSV) as the vector and vehicle of delivery of recombinant virion fragments to confer immunity. This novel technique seems promising for combating norovirus.

While this seems like a promising vaccine, norovirus does not cause a significant amount of mortality, though it does cause some morbidity. It usually lasts for just a day or two and then passes on. Is it worth creating a vaccine against this virus if it doesn’t cause mortality? 


Monday, March 14, 2011

HPV and cervical cancer in South Africa

A recent report published by the WHO about Human Pappiloma Virus is South Africa highlighted the huge risk for women.  The report claimed that 16.84 million women are at risk for developing cervical cancer caused by HPV.   In South Africa about six thousand women are diagnosed with cervical cancer every year.  The real incidence may be much higher since these are merely the diagnosed cases.  Cervical cancer is the second most common cause of cancer in South Africa.  In South Africa, approximately 21% of women are infected with HPV.  The large HIV epidemic is thought to have increased the spread of HPV through immunocompromsed individuals.  Although there is a vaccine for HPV, it is not widely available in South Africa.  This article brings up ethical questions about where money should be spent in resource limited settings.  Should South Africa fund HPV vaccines when they still have a huge need for ARVs?

Hannah Harrison

Gilead’s success slows HIV drug research

Gilead’s success in providing an effective once a day drug for HIV has limited the development of new HIV drugs.  There are fewer drugs in the pipeline now because the market for drugs that need to be taken multiple times a day is much smaller when there is a once a day option.  This poses a problems with the high mutation rate of HIV and the great potential for resistance.  Last year, Atripla, a three drug combination of truvada and Sustiva captured about 40% of the HIV drug market.  The San Francisco Chronicle reported that there were about 100 drugs in various stages of testing in 2006 but there were only 60 drugs in testing in 2010.  Unfortunately, the great success of recent HIV drugs is leading to declines in research because the market is smaller and the competition is fierce. 

Hannah Harrison

Mosquitoes carrying dengue fever

As many of you probably recall, Bob mentioned the appearance of Aedes mosquitoes in Florida.  The potentially fatal disease that many Key West Floridians have been exposed has shown “flu-like” symptoms, but has been more acutely identified as Dengue. At least 46 cases have been reported. This the first substantial outbreak in the continental U.S.. However, because of the harm is threatens to cause, health officials have begun to implement prevention efforts.  Aedes mosquitoes populations are now being tracked and people in the surrounding areas are being educated both about the mosquitoes and the disease. For example, most mosquitoes appear at night and remain outdoors. Thus, screens, staying inside from dusk to dawn, and wearing repellent are all useful techniques. However, aedes mosquitoes tend to live indoors or near the house and bite during the day. Because of the more proximal nature of the aedes mosquitoes, health officials are warning everyone to be particularly vigilant about stagnant water near their homes. One benefit of the aedes mosquitoes’ habits, however, is that they do not travel far during their lifetime. Thus, controlling their populations and their spread should be easier than that of regular mosquitoes.


Sunday, March 13, 2011

Scrapie double-feature.

A report published in the Journal of Virology suggests that scrapie may be transmitted by prion excretion in milk that is ingested by na├»ve suckling lambs. The report also demonstrates that by causing inflammation, lentiviral infection increases prion shedding. These results help to explain sustained prion disease in flocks over generations and warns us about the dangers of administering pooled milk supplement to sheep populations (as if we didn’t already learn this lesson with BSE). 

Another report studied a transgenic mouse system featuring a hamster PrP (HPrP) ORF controlled by the neuron-specific enolase promoter. Expression of HPrP only occurred in brain tissues. The transgenic mice were susceptible to hamster scrapie showing a longer incubation period than observed in normal hamsters. Non-transgenic mice were not susceptible to hamster scrapie. These results indicate that neuron-specific expression of the HPrP minigene will reliably induce susceptibility to hamster scrapie, overcoming the TSE species barrier.

Ligios C. et al. Sheep with scrapie and mastitis transmit infectious prions through the milk. J. Virol. 2001. 85(2):1136-9.

Race R.E. et al. Neuro-specific expression of a hamster prion protein minigene in transgenic mice induces susceptibility to haster scrapie agent. Neuron. 2011. 15(5):1183-91.