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Editorial
Styliani Loukatou1, Paraskevas Fakourelis1, Louis Papageorgiou1,2, Vasileios Megalooikonomou3, Sophia
Kossida1 and Dimitrios Vlachakis1,3
1 Computational Biology & Medicine Group, Biomedical Research Foundation, Academy of Athens, Soranou Efessiou 4,
Athens 11527, Greece
2 Department of Informatics and Telecommunications, National and Kapodistrian University of Athens, University Campus,
Athens, 15784, Greece
3 Computer Engineering and Informatics Department, School of Engineering, University of Patras, 26500 Patras, Greece
Correspondence should be addressed to Dimitrios Vlachakis; Phone: +30 210 6597199, Fax: +30 210 6597545, Email:
dvlachakis@bioacademy.gr
Ebola virus epidemic: a deliberate accident?
The Ebola outbreak
As a new outbreak of Ebola virus has recently taken
place, it is vital that scientists take several steps to-
wards its combat. The Ebola Hemorrhagic Fever out-
break of 2014 is listed as the biggest one in history
with almost 9000 reported human cases and a 53% rate
of fatality. The Ebola virus is classified in the genus of
Ebolovirus, in the family of Filoviridae and order
Mononegavirales (Kuhn et al. 2010). Five viruses of
this class are known to be disease-causing in humans;
Zaire ebolavirus (EBOV), Sudan ebolavirus (SUDV),
Reston ebolavirus (RESTV), Côte d’Ivoire ebolavirus
(TAFV) and Uganda ebolavirus (BDBV). In the case
of the current outbreak, all listed cases have been in-
fected by EBOV. The latter is the most lethal of all. It
was named after the fact that the first formal record
was made in Zaire in 1976, presenting an 88% rate of
fatality; even though 2014’s outbreak is estimated to
be the deadliest Ebola outbreak by far (Gire et al.
2014).
Since 1976, humanity has been compelled to
face Ebola’s disease cases on an approximately annual
basis. At the beginning of the appearance of the dis-
ease, there were cases caused by all viruses’ species.
However, with the passage of time the viruses with the
low fatality rate disappeared. Is this a phenomenon of
natural selection or an artificial outcome? Can we di-
agnose any pattern in this statistical data?
Additionally, the mortality rate has always
increased in underdeveloped countries, probably due to
the lack of an organized health care system. During all
these years the number of human cases has been fluc-
tuating between 1 and 500. The Ebola’s outbreak,
which started in Guinea in December 2013 and spread
among Liberia, Sierra Leone, Nigeria, Senegal and
almost all the West African countries, admeasures
8469 human cases to date (Figure 1). The epidemic
soon spread in the Democratic Republic of Congo and
is still ongoing, with scientists predicting that the cases
could reach the number of 1.4 million by January
(Prevention, October 13, 2014).
Europe and the United States have had the
confidence that Ebola will not spread among their ter-
ritory. Nevertheless, on September 30, the first Ebola
case was diagnosed in Dallas, Texas (McCarthy 2014).
As for the European countries, the first recorded hu-
man case with Ebola was a Spanish missionary who
contracted the virus in Liberia (Gulland 2014). Ger-
many has also recorded the third patient of this deadly
disease and the first human death on October 14. Ac-
cording to the World Health Organization (WHO) in
August 2014, 10241 travelers originating from Sierra
Leone, Guinea and Liberia travelled to European coun-
tries. In addition, large numbers of migrant workers
from the outbreak area are located within Europe and
the US.
The epidemic has not made its presence felt in
Greece yet. However, Reuters reported a scientific re-
search that predicts a 75 percent chance of the virus
being imported into France and a 50 percent chance
into Great Britain by the end of October (Gomes, Sep
2014). Ebola outbreak is expected to accelerate in Oc-
tober 2014 with the number of projected cases touch-
ing the 14000.
Nevertheless, researchers are absolutely confi-
dent that Europe and America will not experience the
nightmare of Ebola’s outbreak. This seems justifiable,
as nearly all of the human cases in developed countries
have been healed. Whoever seeks conspiracy theories
may claim that these countries already have the cure
and that what is taking place in Africa is merely an
experiment. However, hereafter may be a more logical
explanation to oppose these theories.
Nowadays the media are flooded with images
of how humanity deals with the Ebola virus. It is obvi-
Journal of Molecular Biochemistry (2014) 3, 72-76 © The Author(s) 2014. Published by Lorem Ipsum Press.
ous that the range of Ebola cases depends on the pre-
ventive and dealing measures (Muyembe-Tamfum et
al. 1999). In developing countries, due to the lack of
education, expertise and health care, there is a high
transmission and mortality rate. Doctors there do not
have the appropriate medical equipment. They are not
able to run full tests. They do not have the expertise to
treat this epidemic or even to control its spread. People
diagnosed with Ebola should be kept in quarantine in-
dividually, but in West Africa there are barely any
main hospital units. As a result of these, if scientists
have the slightest suspicion of the virus infection in
people “they imprison them in the same cage” (Fowler
et al. 2014).
Culture and traditions can sometimes also
play dramatic roles towards this direction. For in-
stance, several funeral and/or burial rituals require
physical contact with the body of the deceased, even if
he/she has died from Ebola. Physical contact is a cru-
cial communication code among west Africans
(Dowell et al. 1999). Religious beliefs could also aid
in this direction.
On the other hand, developed countries have
all the resources to avoid this epidemic. People can get
informed on how to protect themselves and disease
symptoms are widely known. They have the necessary
educational level in order to resort immediately to
medical aid protecting their health and not putting oth-
ers in risk. In Europe and America, there are special-
ized treatment and hemodialysis units in hospitals.
These countries also have the financial background to
support expensive patient medication (Nagata 2014).
The origin of Ebola
Another subject that may cause a plethora of argu-
ments is that this virus may be a laboratory generated
virus. It may be assumed that all these could be a con-
spiracy or scaremongering theory. Nevertheless, scien-
tists do not know much about this virus except a few
basic characteristics. The virus depletes the body's im-
mune cells and its organs (Sullivan et al. 2011). Not-
withstanding the high fatality rates, there are some
people who survive and recover completely from
EVD’s infections. Furthermore, several research pro-
jects have led to the conclusion that some people may
be explicitly resistant to Ebola infections due to a mu-
tation in the NPC1 gene (Cote et al. 2011). Yet, we
barely know anything about this virus.
For example, it is not completely clear how
Ebola is transmitted. There is a conjecture that the vi-
rus is transmitted to people from wild animals. How-
ever, by reason of the high mortality among them, it is
impossible that these animals are the reservoir host of
EVD. The conviction is that fruit bats of the pteropodi-
dae family are natural Ebola virus hosts even though
the reservoir of EVD has not yet been identified
(Groseth et al. 2007). It is also believed that, among
73 Journal of Molecular Biochemistry, 2013
Figure 1. World prevalence of Ebola outbreak. Data are totals and only include confirmed cases (colored blue) and case deaths
(colored red). Data are based on official information reported by the Ministries of Health up to October 14 2014 (WHO, 2014).
humans, EVD can be disseminated through direct con-
tact with blood or body fluids such as sweat, urine,
breast milk, saliva and vomit of an infected person
(Francesconi et al. 2003).
There are some not well known dark sides of
EVD though, such as the potential use in biological
warfare. This encompasses the use of biological infec-
tious agents as weapons in order to nullify or extermi-
nate humans, animals or plants. The target can range
from one single individual to an entire population.
Based on the merits, biological warfare represents an
act of an invisible war. In these battlefields there is no
need of troop reinforcements or heavy weapons. These
wars do not require colossal financial resources, due to
the fact that a biological weapon acts underground and
it can be transferred easily through water, through the
ground or through the air without being perceived by
anybody.
So the ability to disseminate disease through
aerosol or airborne small-droplet nuclei would render
filoviruses a potential biologic warfare threat
(Salvaggio & Baddley 2004). According to some re-
searchers who have been involved with Soviet biologi-
cal weapons, Ebola and some other viruses have been
already weaponized in this manner by the former So-
viet Union (Miller et al. 2002). Aerosol transmission
of EVD has been demonstrated in experimental models
involving nonhuman primates (Borio et al. 2002). Dur-
ing an experiment to evaluate the benefits of interferon
treatment following infection with EBO-Z, two out of
three control rhesus monkeys became ill. Researchers
were unable to document direct or percutaneous con-
tact through injections, and speculated that inoculation
to the control animals occurred via pulmonary, naso-
pharyngeal, oral or conjunctival routes (Jaax et al.
1995). Definitive evidence that small-droplet nuclei
pose a substantial transmission risk among humans
during naturally occurring outbreaks is lacking. After
making a quick comparison of the number of cases
between this outbreak and previous ones, one could
argue that something is different this time (Salvaggio
& Baddley 2004). Is this epidemic disease a genuine
natural disaster or something else?
Diagnosis, treatment and EBOV proteins
In accordance with what is known so far, the
symptoms occur between 2 to 21 days after the infec-
tion. Typically, early symptoms include fever, head-
ache, weakness, stomach disorders, joint and muscle
pains (Bwaka et al. 1999). At a later stage, the patient
may present cough, breathing difficulties, hiccups,
bloodshot eyes and internal-external bleeding. There is
no treatment or vaccines to date. Hence, every research
project on this virus will constitute a significant pro-
gress towards the identification of Ebola’s mecha-
nisms.
The diagnosis of Ebola’s infection is labor-
intensive, as its symptoms are similar to other diseases,
such as cholera and malaria. Even the symptoms of a
common flu can be confused with those of Ebola. Di-
agnostic methods include CBC, electrolytes, blood
tests, liver tests and virus-specific antibodies (Tigabu
et al. 2009). The genome of EBOV is roughly 19 kb
long. It encodes seven structural proteins; RNA poly-
merase, nucleoprotein (NP), polymerase cofactors
VP35 and VP40, GP as well as transcription activators
VP30 and VP24 (Huang et al. 2002). It has been
shown from a plethora of research projects that this
protein is an antagonist of type one interferons and that
VP35 interacts with the IRF-3 kinases IKKε and TBK-
1. Its function is to prevent the establishment of a cel-
lular antiviral state by blocking virus-induced phos-
phorylation and triggering the activation of the inter-
feron regulatory factor 3 (IRF3) (Basler et al. 2003).
IRF3 is a transcription factor which plays a significant
role in the induction of interferons alpha and beta (IFN
-α/β).VP35 possesses a carboxy-terminal domain with
a unique fold that allows double-stranded RNA
(dsRNA) binding (Cardenas et al. 2006). This may be
a necessary function for the inhibition of IFN-α/β pro-
duction. Furthermore, VP35 mutants missing the
coiled-coil motif or carrying a mutation designed to
disrupt coiled-coil function were defective in the for-
mation of an oligomer. Of note, VP35 is also related
with the H1N1 and Margburg virus (Basler et al.
2000). In contrast, we do not know if VP35 is phos-
phorylated, although it is thought to share the function
of the phosphorylated proteins of rhabdoviruses and
paramyxoviruses due to its position in the genome.
Future directions
The full crystal structure of the Zaire EBOV
VP35 is not available yet. However, only recently the
structure of the Zaire EBOV VP35 interferon inhibi-
tory domain (IID) has been established. In the free
form the Zaire EBOV VP35 IID bounds to dsRNA.
VP35 IID forms a unique fold with 2 basic residue
clusters. One of these clusters is important for dsRNA
binding (Leung et al. 2010). The cluster of dsRNA that
function to bind is centered on Arg-312. It is a required
conserved residue for IFN inhibition. The C-terminal
cluster of basic amino acids of Ebola virus VP35 is a
prerequisite in order to bind the dsRNA with the inter-
feron regulatory factor 3 (IRF3) and inhibit its func-
tionality. Finally, VP35 is assumed to block and re-
verse the activation of protein kinase R (PKR).
Journal of Molecular Biochemistry, 2013 74
There is a dear need for a full structural 3D
model of VP35 (Carvalho et al. 2013, Dalkas et al.
2013, Vlachakis et al. 2014, Vlachakis & Kossida,
2013). There are preliminary indications of allosteric
sites on its structural domains, which could be ex-
ploited for the designing customized drug-like inhibi-
tors (Vlachakis et al. 2014, Loukatou et al. 2014, Pa-
pangelopoulos et al. 2014, Papageorgiou et al. 2014,
Sellis et al. 2009, Vangelatos et al. 2009). Funds must
be allocated towards the functional and biochemical
characterization of viral proteins such as VP35, which
constitute necessary machinery for Ebola’s virulence.
It is absolutely crucial to dig deeper, investigate and
understand the molecular mechanisms, which underlie
the rather complicated nature of this viral species.
Conficts of Interest
The authors declare no conflicts of interest.
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