Hot off the press: ebola structure and sick pigs

Iremember as I struggled through my PhD in the 1980s wondering what the lab next door was up to as I never saw anyone there in a lab-coat. No-one there struggled with vast cell cultures to get a few ug of material as I did or God forbid had to proactively source chicken hearts from a kosha chicken processing factory. I often wished for an old fashioned milk maid's yoke as I wandered to the lift with buckets either side heavily laden with Winchesters of cells. The lift was opposite their lab and oh how lucky they seemed. They weren't electron microscopists but they too spent an awful lot of time locked in a small room but on computer programmes so I ended up asking. They were one of the first groups doing computer modelling of proteins with the longterm goal of being able to look at protein interactions and potentially do drug discovery without actually involving animal testing .


How times have changed: computer modelling of proteins to identify potential binding sites for drugs is common practice.

And today I heard that this could now be applied to the Ebola virus, thanks to a team in Iowa (1) . They've made that first important step. Using X-ray crystallography and nuclear magnetic resonance spectroscopy, a team led by Gaya Amarasinghe, have solved the structure of a key part of the VP35 protein: this protein interferes with the hosts first line of defense to invading organsims including viruses, the so-called innate immune response. With this key part of VP35 structure available, they can use this structure to identify and design drugs that could bind with the VP35, inhibit its function and so potentially neutralise ebola virus.

So what,you say, and I say where have you been living…there is currently no vaccine for human ebolavirus infection, ebolavirus along with its fellow filoviruses, marburg and lassa, causes haemorrhagic fever, high tech treatment is your only hope and the mortality rate is 50-90%. Outbreaks occur regularly in Africa( usually Sudan and Democratic Republic of Congo) , in people living close to forest edges: the initial case will be due to eating/handling infected primates (wild apes such as gorillas) and it is then transmitted person to person .but there is also a link to mining activities. More info can be found on the WHO site (2)

So horrible and frightening is Ebola, it made it to Hollywood with Dustin Hoffman leading his CDC team in a fight against an outbreak clearly modelled on Ebola and its ilk and because of its importance I chose it for the front cover of the journal I edit, Tropical Diseases Bulletin.

You can read more about ebola and the information on it in Global Health but here is a little something to bring you up to date.

AS I said outbreaks in Africa were associated with close contact with wild apes, usually dead or ill, through encroachment on their habitat such as mining activities or through hunting for & consumption of bushmeat (the meat here being ape). The bushmeat trade is now international so there is the potential for spread outside Africa . Then there is tourism, and thereby hangs a tale… because apes were not thought to be the chief reservoir…fruit bats had long been suspected, bats in tree roosts and bats in mines.

Bats when they eat spit out partially digested fruit and insects. Nipah, Hendra, SARS and potentially Ebola viruses could all be harboured by fruit bats, the bats roost in trees, and drop their food which is then eaten by livestock or gorillas who shelter beneath. And thus Ebola via the gorillas could infect man (3).

But in 2005, 3 species of fruit bats, all locally eaten, were shown to harbour ebola So that's another route and then there are those mines. In 2008, a Dutch tourist died from marburg virus contracted through visiting a mine in Uganda in that June where she was exposed to fruit bats. The bats in this cave are thought to be of the same species which had been found to carry asymptomatically the Zaire strain of ebolavirus and the marburg virus found to carry filoviruses(4,5,6)

Of course local miners had died from marburg virus before but nothing concentrates the international mind so wonderfully if it involves a tourist.

Now lets consider sick pigs. What have they got to offer the ebola story. Well apparently a form of ebola (ebola-reston)was imported in monkeys supplied from the Philippines into the USA to a place called Reston (hence the name). Its not harmful to people but kills monkeys. In October 2008, they found it in pigs for the first time, once more in the Philippines (7). Oh dear…its crossing the species barrier.

Ebolavirus is classed as an emerging infectious disease, is one of the MDG6 infectious diseases, it has been considered as potentially pandemic risk alongside SARS and Avian flu. And its listed as a potential bioterror weapon.
Sweet dreams.

References

  1.  Iowa State University researchers discover structure of key Ebola protein

  2. WHO ebola website 

  3. What Links Bats to Emerging Infectious Diseases?

  4. Studies of reservoir hosts for Marburg virus. 

  5. Marburg hemorrhagic fever associated with multiple genetic lineages of virus. 

  6. Marburg virus infection detected in a common African bat.

  7. Ebola Reston found in domestic pigs in the Philippines 

 

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