Friday, March 25, 2016

I'm Not Dying, I'm Just Reston

Ebola Virus - Credit CDC


Planned, or not, there are some legitimate studies that are just destined to capture the media's interest.  Curing cancer, or the common cold, of course. But creating or enhancing a flu virus to make it deadlier, or finding a plausible route by which a benign virus could mutate and kill us all, are also guaranteed headline generators.

After all, the media loves stories where they can use the word `mutate' or `mutations' in it.  And if it involves a virus like H5N1 or Ebola, so much the better.

Which is why, overnight, the media has been filled with headline variations of:

For the discerning reader, the operative word in the above headline is `May'.

The study centers on Ebola Reston - notable for not being pathogenic in humans - and involves side by side comparison of its genetic structure to the four other highly pathogenic Ebola strains, looking for subtle differences that might account for its lack of pathogenicity in humans.

`May' is used 18 times in the actual study (`likely to' appears 10 times), and while these slippery modifiers don't invalidate the study's findings, they do remind us there are still an awful lot of unknowns here.

Researchers found relatively few differences between Reston and the deadlier strains, and by focusing on key areas of the virus they believe affects the virulence of the virus in a human host, the authors have concluded that only a few changes in one Ebola virus protein (VP24) may be needed to turn Ebola Reston into a virus that can cause human disease.

A decade ago we were warned that H5N1 was (take your pick) 5, 3, or as little as 1 mutation away from becoming a pandemic strain, and that hasn't happened yet.

So these sorts of assessments - while of genuine scientific interest - aren't necessarily predictive of future events.

The study itself may be read in its entirety at the link below.  When you return, I'll have a bit more on the history, and mystery, of Ebola Reston.

Scientific Reports 6, Article number: 23743 (2016)
Published online:


Reston viruses are the only Ebolaviruses that are not pathogenic in humans. We analyzed 196 Ebolavirus genomes and identified specificity determining positions (SDPs) in all nine Ebolavirus proteins that distinguish Reston viruses from the four human pathogenic Ebolaviruses. A subset of these SDPs will explain the differences in human pathogenicity between Reston and the other four ebolavirus species. Structural analysis was performed to identify those SDPs that are likely to have a functional effect. 

This analysis revealed novel functional insights in particular for Ebolavirus proteins VP40 and VP24. The VP40 SDP P85T interferes with VP40 function by altering octamer formation. The VP40 SDP Q245P affects the structure and hydrophobic core of the protein and consequently protein function. Three VP24 SDPs (T131S, M136L, Q139R) are likely to impair VP24 binding to human karyopherin alpha5 (KPNA5) and therefore inhibition of interferon signaling. 

Since VP24 is critical for Ebolavirus adaptation to novel hosts, and only a few SDPs distinguish Reston virus VP24 from VP24 of other Ebolaviruses, human pathogenic Reston viruses may emerge. This is of concern since Reston viruses circulate in domestic pigs and can infect humans, possibly via airborne transmission. 

Ebola Reston is one of five known Ebola virus species, and the only one found to be endemic outside of Africa.
Unlike its African cousins, Ebola Reston – while capable of infecting humans – is not known to produce illness or death in man.  It can, however, produce serious illness in non-human primates, and can infect  pigs (generally asymptomatically).

Ebola Reston was first discovered in crab-eating macaques, imported from the Philippines, at a research laboratory in Reston, Virginia (USA) (hence the name) in 1989. This discovery was recounted somewhat sensationally in the book, The Hot Zone, by Richard Preston.

In late 2008 Ebola Reston made another high profile appearance when it was reported for the first time in pigs, again from the Philippines.  This from the FAO
First detection of Ebola-Reston virus in pigs
FAO/OIE/WHO offer assistance to the Philippines
Manila/Roma, 23 December 2008 - Following the detection of the Ebola-Reston virus in pigs in the Philippines, FAO, the World Organization for Animal Health (OIE) and the World Health Organization (WHO) announced today that the government of the Philippines has requested the three agencies send an expert mission to work with human and animal health experts in the Philippines to further investigate the situation.

An increase in pig mortality on swine farms in the provinces of Nueva Ecija and Bulacan in 2007 and 2008 prompted the Government of the Philippines to initiate laboratory investigations. Samples taken from ill pigs in May, June and September 2008 were sent to international reference laboratories which confirmed in late October that the pigs were infected with a highly virulent strain of Porcine reproductive and respiratory syndrome (PRRS) as well as the Ebola-Reston virus.
(Continue . . .)

Roughly a month later, we learned that several farm workers in contact with infected pigs tested positive for antibodies to the Ebola-Reston virus.  None displayed any signs of illness (see Ebola Reston in pigs and humans in the Philippines)

The risks to human health are believed low with Ebola Reston, although there is relatively limited experience dealing with this virus. The World Health Organization hedges its bets slightly with Ebola Reston by stating:

Among workers in contact with monkeys or pigs infected with Reston ebolavirus, several infections have been documented in people who were clinically asymptomatic. Thus, RESTV appears less capable of causing disease in humans than other Ebola species.

However, the only available evidence available comes from healthy adult males. It would be premature to extrapolate the health effects of the virus to all population groups, such as immuno-compromised persons, persons with underlying medical conditions, pregnant women and children. More studies of RESTV are needed before definitive conclusions can be drawn about the pathogenicity and virulence of this virus in humans.

As to whether Ebola Reston could someday mutate into a more dangerous form, the answer is that it probably can. Viruses mutate, and given enough time and enough rolls of the genetic dice, increased virulence is always possible.

As to how likely that is to happen, or when, the truth is scientists haven't had a lot of success in predicting if or when a virus is about to break bad.

Maybe, though . . . with enough research . . . 

In the meantime, even though human illness has never been reported with Ebola Reston infection, the WHO advises people working in areas where they might be exposed to give the virus some respect:

Controlling Reston ebolavirus in domestic animals

No animal vaccine against RESTV is available. Routine cleaning and disinfection of pig or monkey farms (with sodium hypochlorite or other detergents) should be effective in inactivating the virus.

If an outbreak is suspected, the premises should be quarantined immediately. Culling of infected animals, with close supervision of burial or incineration of carcasses, may be necessary to reduce the risk of animal-to-human transmission. Restricting or banning the movement of animals from infected farms to other areas can reduce the spread of the disease.

As RESTV outbreaks in pigs and monkeys have preceded human infections, the establishment of an active animal health surveillance system to detect new cases is essential in providing early warning for veterinary and human public health authorities.