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The knowledge of biotechnology increases the risk of using biochemical weapons for mass destruction. Prions are unprecedented infectious pathogens that cause a group of fatal neurodegenerative diseases by a novel mechanism. They are transmissible particles that are devoid of nucleic acid. Due to their singular characteristics, Prions emerge as potential danger since they can be used in the development of such weapons. Prions cause fatal infectious diseases, and to date there is no therapeutic or prophylactic approach against these diseases. Furthermore, Prions are resistant to food-preparation treatments such as high heat and can find their way from the digestive system into the nervous system; recombinant Prions are infectious either bound to soil particles or in aerosols. Therefore, lethal Prions can be developed by malicious researchers who could use it to attack political enemies since such weapons cause diseases that could be above suspicion.
(A) Illustration of the normal structure of human Prion protein gene (PRNP). PrPc is synthesized from a 254 amino acid precursor. The nascent peptide is cleaved at both the N-and C-terminal in the Endoplasmic Reticulum (ER). A glycosylphosphatidylinositol anchor (GPI) (purple) is attached to the C-terminus at position 231 of PrPc that helps link it to the extracellular membrane (lipid bilayer).In the Golgi, PrPc is N-glycoslyated at positions 181 and 197. Mature PrPc consists of the amino acid residues 23-231 and is expressed as a membrane glycoprotein anchored to the cell surface by a GPI moiety. (H) and (S) indicate α-helix and β-strandregions, respectively. (S-S) and (Y) "inverted" indicate a disulfide bond and N-glycosylation sites, respectively. (OR) specific octapeptide repeat. (B) Mature PrPc dimer. Under native conditions, part of the native bovine PrPc exists as a monomer-dimer equilibrium. It is theorized from this dimeric structure that the dimerization is the first step in amyloid formation and the presence of these dimers could possibly speed up the aggregation of PrPSc. (C) The mature human PrPc protein. (B and C) NH2-terminal (letter N in Figure), COOH-terminal (letter C in Figure), α-helix (H1-H3) and β-strand (S1 and S2 in Figure). (D) A model for fibrils of fungal HET-s Prion forming domain. Since no structural data for PrPSc have been reported to date, this is shown for comparison. The organization of this fibril is a left-handed β-solenoid with dense, parallel β-sheet packing. The β-solenoid fold has been proposed for PrPSc. (A) Courtesy of Cayman Chemical Company. Ann Arbor, Michigan. USA. (B-C) Adapted From: Sekijima, M. Molecular dynamics simulation of dimeric and monomeric forms of human Prion protein: insight into dynamics and properties. Biophys J. With permission. (D) Adapted From: Wasmer, C. Amyloid fibrils of the HET-s(218-289) Prion form a beta solenoid with a triangular hydrophobic core. Science. With permission.
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Food Sci. Technol, Campinas, 34(3): 433-440, July-Sept. 2014
Food Science and Technology ISSN 0101-2061
Received 08 Apr., 2014
Accepted 09 July, 2014 (006342)
1Federal University of São Paulo – UNIFESP, Botucatu, SP, Brazil, e-mail: ericalmeida2000@yahoo.com.br
*Corresponding author
Prions: the danger of biochemical weapons
Eric Almeida XAVIER1*
1 Introduction
People have had a passion for weapons of mass destruction
since the government military agencies search for chemical
weapons culminating with the use of poisonous gases in the First
War. During the Cold War, there were many rumors of research
on biochemical and biological weapons since intelligence
agencies of North America and Russian, used dierent types
of weapons, such as radioactive, poison and contagious disease
weapons, agaist their political enemies because these weapons
cause diseases that could be above suspicion. It is important to
emphasize that Prions also have this characteristic. erefore
it is plausible that Prion weapons can be used not only by
governments but also by terrorists.
Furthermore, hypothetically, if Prions were used as a
biochemical weapon, they could damage not only humans and
animals, but the worldwide economies; therefore, even if Prions
do not kill instantly a target, they can be a very persuasive object
for those who have access to it.Prion diseases include a group
of fatal neurodegenerative and infectious disorders in humans
such as Creutzfeldt-Jacob disease (CJD), a variant form of CJD
(vCJD), Gerstmann-Sträussler-Scheinker syndrome (GSS), and
kuru, fatal familial insomnia (FFI); in animals, they include:
scrapie of sheep and goats, chronic wasting disease (CWD)
of mule deer and elk, and bovine spongiform encephalopathy
(BSE) of cattle (Prusiner, 1996). e central feature of these
disorders is the conformational change of the host encoded,
cellular Prion protein (PrPc), see figures(Figure1A and
Figure2B, C) to an abnormal, partially proteinase K resistant
and infectious isoform (PrPSc) with an aggregation propensity
accumulating in the brain of diseased individuals (Figure1B
and Figure2D) (Gambettietal., 2003; Tatzelt & Schätzl, 2007).
Cases of vCJD in Great Britain and France raised the possibility
that BSE has been transmitted to humans (Batemanetal., 1995;
Cousensetal., 1997). Macaque monkeys and marmosets both
developed neurologic disease several years aer inoculation
with bovine Prions (Bakeretal., 1993; Onoetal., 2011). ese
experiments clearly show that the inoculation of Prions is
potentially fatal, and the fact that Prion strains are transmitted
between species raised the possibility that a large section of
the population is at high risk as a result of exposure to BSE
Prions (Andersonetal., 1996; Sweetingetal., 2010; Bruceetal.,
1997; Collingeetal., 1996; Grin, 1997; Lasmézasetal., 1996;
Scottetal., 1993).
Prions have key features which help them to survive in the
environment for long periods, such as the resistance to protein
degradation, “partially resistant to proteinase K” (Boltonetal.,
1982; Prusiner, 1991), high resistant when exposed to
irradiation, heat, and harsh chemical treatments (Plum, 1997),
plus the fact that they can be attached to soil (Johnsonetal.,
2006; Saundersetal., 2011a) and spread through air, and
therefore they are extremely hazardous (Denkersetal., 2010).
Although Prions are just only a polypeptide sequence, they are
resistant to heat since people who consumed contaminated
meat aer preparation got sick; this raised the possibility that
a particular conformation of bovine PrPSc was selected for
heat resistance during the manufacture of meat and bone meal
(MBM). erefore, it is believed that MBM is the source of
Prions responsible for BSE (Prusiner, 1997).
erefore, hypothetically, Prions can be manufactured
based on the molecular characteristics of the Prion protein
to make deadly biochemical weapons. e study on how the
conversion of PrPC (the normal cellular protein) into PrPSc
(the abnormal disease-causing isoform) (Supattapone, 2010)
can generate polypeptide sequences designed exclusively to kill.
Basically, an ideal Prion polypeptide sequence to be used as a
biochemical weapon must be easily recombined and produced
in large scale (Supattapone, 2010), be resistant to cold and heat,
be fatal in very small quantities, and be transmitted through
air, as demonstrated by (Denkersetal., 2010; Haybaecketal.,
2011), and through water, food andsoil, as demonstrated
Abstract
e knowledge of biotechnology increases the risk of using biochemical weapons for mass destruction. Prions are unprecedented
infectious pathogens that cause a group of fatal neurodegenerative diseases by a novel mechanism. ey are transmissible
particles that are devoid of nucleic acid. Due to their singular characteristics, Prions emerge as potential danger since they
can be used in the development of such weapons. Prions cause fatal infectious diseases, and to date there is no therapeutic or
prophylactic approach against these diseases. Furthermore, Prions are resistant to food-preparation treatments such as high
heat and can nd their way from the digestive system into the nervous system; recombinant Prions are infectious either bound
to soil particles or in aerosols. erefore, lethal Prions can be developed by malicious researchers who could use it to attack
political enemies since such weapons cause diseases that could be above suspicion.
Keywords: Prions; biochemical weapons; Prion diseases; Prions danger to the environment; Prions risk alert.
OI:Dhttp://dx.doi.org/10.1590/1678-457X.6342
Food Sci. Technol, Campinas, 34(3): 433-440, July-Sept. 2014
434
Risk of biochemical weapons
is a possible mechanism for triggering the conversion of
PrPc into PrPSc where α-helices appear to be converted into
β-sheets (Zhanget al., 1995). However, no atomic-resolution
structure of the brillar state, which is likely to be infectious,
has been reported to date because characterizingthe structure
of PrPSc has been challenging due to the diculty in studying
it through Nuclear magnetic resonance (NMR) or X-ray
crystallography methods (Wasmeretal., 2008). However,there
isa structural model based on solid-state nuclear magnetic
resonance restraints for amyloid brils from the Prion-forming
domain (residues 218 to 289) of the HET-s (het-s/S locus)
that occur naturally in the filamentous fungus Podospora
anserine (Figure2D) (Wasmeretal., 2008; Dalstraetal., 2005).
Nevertheless, the basis of PrPSc conversion has been elucidated.
Some models with the earliest conversion events involving
PrPSc have been established suggesting that the formation of
the disease-causing isoform involves refolding in two of the PrPc
NH2-terminal (N-terminal) α-helix (H1and H2) into β-sheets
or the two β-strands (S1 and S2) and proposing to “seed” β-sheet
elongation as the short α-helix H1 (Figure1) (Huanget al.,
1996; Muramotoetal., 1996); the single disulde bond joining
COOH-terminal helices (C-terminal) would remain intact
because the disulde is required for PrPSc formation (Figure1)
(Panetal., 1993; Muramotoetal., 1996).
by (Saunderset al., 2009; Saundersetal., 2011a), Gough &
Maddison (2010) and (Smithetal., 2011). If Prions do not meet
all specications necessary of a biochemical weapon to kill,
they at least have key features such as surviving through the
digestive system, as demonstrated by Sales (2006), resistance to
high temperatures during food preparation processes (Prusiner,
1997), recombinant Prions are infectious, as demonstrated by
(Wangetal., 2010; Legnameetal., 2004; Makaravaetal., 2010),
and lastly, a few molecules can produce a chain reaction in the
conversion of PrPc into PrPSc causing a fatal neurodegenerative
disease (Rigteretal. 2009).
2 Prion molecular factorsinvolved inthe conversion
of thenative form PrPcintotheinfective form PrPSc,
which could be explored for evil plans
The basic mechanisms involved inthe conversion
PrPcinto PrPSc are mainly achieved in four routes: the
first includes the conformational mechanisms; the second
includes the structural mechanisms; the third is related to the
environmental pH; and fourth is the pathologic route.
e rst route is associated to the lethality of the peptides,
which involves a conformational change, through which the
alfa (α)-helical content diminishes and the amount of beta
(β)-sheet increases (Panet al., 1993). PrPSc formation is a
posttranslational process involving only a conformational
change in PrPC. A comparison of the secondary structures
shows that PrPc is 42% α-helical with a very low (3%)β-sheet
content, whereasPrPSc consists of 30%α-helices and
43%β-sheets (Figure1). Although the precise physiological
role of PrPScand the chemical dierences betweenPrPSc and
normal Prion protein (PrP) remain unknown, it appears that
the dierences are conformational (Prusiner, 1998). e Prions
conformational transition from PrPc to PrPSc is accompanied
by profound changes in the properties of the protein: PrPc is
soluble in nondenaturing detergents, whereas PrPSc is not
(Meyeretal., 1986) and PrPC is readily digested by proteases,
whereas PrPSc is partially resistant (Kociskoet al., 1994;
Hsiaoetal., 1989) (Figure1B). However, it is not fullyknown
how disease-causing Prions arise in patients with sporadic
forms; the main hypothesis is the horizontal transmission of
Prions from humans or animals (Haleyetal., 2011). erefore it
seems that the diseases caused by Prions are diseases of dietary
origin, raising a great possibility that the PrPSc conformation
is highly resistant to the mechanisms of animal polypeptides
digestion, which is a key feature for a biochemical weapon (Sales,
2006). e second route is the structural mechanisms, which
are associated with the basic structural transition from PrPc
to PrPSc. Peptide fragments corresponding to Syrian hamster
PrP residues 90 to 145 and 109 to 141, which contain the most
conserved residues of the Prion protein and the rst two putative
α-helical regions, were studied using infrared spectroscopy
and circular dichroism. e peptides could be induced to form
α-helical structures in aqueous solutions and in the presence
of organic solvents such as triuoroethano or detergents such
as sodium dodecyl. On the other hand, NaCl at physiological
concentration or acetonitrile induced the peptides to acquire
substantial β-sheet. e results suggest that perturbation of
the packing environment of the highly conserved residues
Figure1. (A) Normal Human Prion protein (HuPrP) with 43% of
α-helix, sensitive to proteinase K treatment without forming aggregates.
e NH2-terminal (letter N in Figure) region (residues 23–124) is
exible, and the COOH-terminal (letter C in Figure) region (residues
125–228) that contains the globular domains is well structured the
structures contain intramolecular disulde bridge (S-Syellow trace
in Figure), three α-helices, (H1), (H2), and (H3), red color, and a
short double-stranded β-sheet (S1) and (S2). (H) and (S) indicate
α-helix and β-strand, respectively (indicated by the blue arrows), and
a disulde bridge S-S(trace). (B) Human Prion protein infectious
isoform (HuPrPSc) with 30% of α-helix and 43% of β-sheet, resistant
to proteinase K treatment and capable of forming aggregates. e two
β-strands (S1) and (S2) are proposed to “seed” β-sheet elongat ion (gray
and blue colors) as the short α-helix (H1) unfolds and is converted
into the PrPSc conformation. (H2) and (H3) remain stabilized via
linkage of a disulde bridge (yellow trace). (B) α-helix (red color),
β-sheet elongation (gray and blue colors), and disulde bridge S-S
(yellow trace). Courtesy of Cayman Chemical Company. Ann Arbor,
Michigan. USA.
Food Sci. Technol, Campinas, 34(3): 433-440, July-Sept. 2014 435
Xavier
pH 4.1 can convert into the β-sheet conformation at pH 3.6
but not vice versa a loss of α-helix since the gain of β-sheets
and a number of PrPSc-like conformations can be generated
by incubating recombinant PrPcat low pH, indicating that
the protonation of key residues is likely to destabilize PrPc
facilitating its conversion to PrPSc. Fold stability of human PrPc
as a function of pH is signicantly reduced by the protonation
of two histidine residues, His187 and His155. Mutation of
His187 to an arginine imposes a permanently positively charged
residue in this region of the protein and has a dramatic eect
on the folding of PrPc resulting in a molecule that displays a
markedly increased propensity to oligomerize. e oligomeric
form is characterized by an increased β-sheet content, loss of
xed side chain interactions, and partial proteinase resistance.
erefore, the protonation state of H187 appears to be crucial
in determining the conformation of PrP; the unprotonated
form favors native PrPc, while the protonated form favors
PrPSc-like conformations (Hosszu etal., 2010; Gerberetal.,
2008; Hosszuetal., 2009). If these conditions are relevant, as
there is considerable evidence that endosome-like organelles or
Theoretically, the high β-sheet content of PrPSc was
predicted based on its ability to polymerize into amyloid brils
(Prusineretal.,1983; Caugheyetal., 1991). Studies have found
that the deletion of each of the four predicted helices prevented
PrPSc formation, as did the deletion of the stop transfer eector
region and the C178A mutation. e removal of a 36-residue
loop between helices 2 and 3 did not prevent formation of
protease-resistant PrP; the resultingscrapie-likeprotein,
designated PrPSc106, contained106 residues aer cleavage
of an N-terminal signal peptide and a C-terminal sequence
for glycolipid anchor addition.e addition of the detergent
Sarkosyl to cell lysates solubilized PrPSc106, which retained
resistance to digestion by proteinase K. ese results suggest
that the regions of a proposed secondary structure in PrP
and the disulde bond stabilizing helices 2 and 3are required
for PrPScformation (Rogersetal., 1993; Fischer etal., 1996;
Muramotoet al., 1996). e third route is related to the pH
environment. e pHseems to be important forthe change
ofconformation because human PrPc has a pH-dependent
conformational change. e α-helical intermediate formed at
Figure2. (A) Illustration of the normal structure of human Prion protein gene (PRNP). PrPc is synthesized from a 254 amino acid precursor.
e nascent peptide is cleaved at both the N-and C-terminal in the Endoplasmic Reticulum (ER). A glycosylphosphatidylinositol anchor (GPI)
(purple) is attached to the C-terminus at position 231 of PrPc that helps link it to the extracellular membrane (lipid bilayer).In the Golgi, PrPc is
N-glycoslyated at positions 181 and 197. Mature PrPc consists of the amino acid residues 23-231 and is expressed as a membrane glycoprotein
anchored to the cell surface by a GPI moiety. (H) and (S) indicate α-helix and β-strandregions, respectively. (S-S) and (Y) “inverted” indicate a
disulde bond and N-glycosylation sites, respectively. (OR) specic octapeptide repeat. (B) Mature PrPc dimer. Under native conditions, part of
the native bovine PrPcexists as a monomer-dimer equilibrium. It is theorized from this dimeric structure that the dimerization is the rst step
in amyloid formation and the presence of these dimers could possibly speed up the aggregation of PrPSc. (C) e mature human PrPc protein.
(BandC) NH2-terminal (letter N in Figure), COOH-terminal (letter C in Figure), α-helix (H1-H3) and β-strand (S1 and S2 in Figure). (D) A
model for brils of fungal HET-s Prion forming domain. Since no structural data for PrPSc have been reported to date, this is shown for comparison.
e organization of this bril is a le-handed β-solenoid with dense, parallel β-sheet packing. e β-solenoid fold has been proposed for PrPSc.
(A) Courtesy of Cayman Chemical Company. Ann Arbor, Michigan. USA. (B-C) Adapted From: Sekijima, M. Molecular dynamics simulation
of dimeric and monomeric forms of human Prion protein: insight into dynamics and properties. Biophys J. With permission. (D) Adapted From:
Wasmer, C. Amyloid brils of the HET-s(218-289) Prion form a beta solenoid with a triangular hydrophobic core. Science. With permission.
Food Sci. Technol, Campinas, 34(3): 433-440, July-Sept. 2014
436
Risk of biochemical weapons
for all of the transport of Prions, and other cells, including
tingible-body macrophages (phagocytic cells in lymphoid
germinal centers) are plausible locations for PrPSc propagation
(Arnoldetal., 1995; Aguzzi & Sigurdson, 2004) since PrP is
captured by phagocytes of the immune system.erefore, the
conformational convertion of PrPc into PrPSc can be triggered
by endocytosis of a Prion particle, and a phagocytic cell may
trigger the disease with a particle reaching the brain by the
sympathetic nervous system from the lymphatic tissues (Harris
& True, 2006; Aguzzietal., 2008; Aguzzietal., 2001; Venneti,
2010). Therefore, the immune system is a target of lethal
Prions, which could be added to adjuvants that are intended to
perform phagocytosis by DCs to increase their eciency and
thus be transmitted through small wounds or scratches on the
victim’s skin.
3 Discussion
Recombinant Prions with fatal features could be developed
in relatively simple laboratories using animals such as rats,
mice, and monkeys (Supattapone, 2010; Wang et al., 2010;
Legnameetal., 2004; Makaravaetal., 2010). Ricin has already
been used as a weapon (Augerson, 2000; National Security Notes,
2004), for example in the case that caught the full attention of
international media and was described by Papaloucas et al
(2008) and which was about a political dissident that was killed
by a supposed KGB agent using a single ricin-tipped umbrella
as a weapon. Consequently, the same mechanism can be used to
deliver Prions using simple objects without giving the victim a
chance to receive a vaccine, treatment, or a specic anti-serum
injection. Some political enemies must be eliminated and Prions
can be a possible alternative to the use of venoms, precisely
because Prions do not kill instantly and make the investigation
process very dicult to trace the assassin agent. Another class
of venom that have been used before and can be substituted by
Prions are the radioactive venom (Jordan & Finn, 2006) because
Prions can cause the same eect. One advantage is leaving no
traces detectableby anti-gama radiation equipment, such as
Geiger counter, and another advantage is being less dangerous
to the assassin agent willing to use it.
e psychological eect caused by the use of Prions to
extinguish rivals could be as powerful as the radioactive eects,
and it can send a strong message such as “Do not play with the
government interests”. e use of such weapons seems to have
strong personal issues involved because it would be easier to
kill someone simply using a gun, but with Prions, the victim
agonizes for months before dying (Papaloucasetal., 2008). e
most frightening possibility would be the use of Prions to get
rid of enemies in large regions ofongoingconicts or political
separatist wars. In theory, it would not raise any suspicion by
the international community because of its silence mechanisms,
but aer years a lot of people would start dying presenting the
same symptoms and the alert would have come too late. If
Prions are made in laboratories with the purpose to be spread
in the air, it could kill a large number of people since it has
been demonstrated that CWD can be dispersed as aerosol
(Denkersetal., 2010; Haybaecketal., 2011; Fordetal., 2002).
In addition, the decontamination of the environment can be a
lysosomes, with their locally acidic environments are plausible
locations for PrPSc propagation (Arnoldet al., 1995), these
models of Prions for these molecular regions are crucial for the
development of disease via PrPSc, and theerefore the structure
of these regions of the molecule can be exploited as a catalytic
core for elaboration of new lethal Prions. Exploring mechanisms
that allow the Prions to be captured by the airways as an aerosol
microparticles; thus lesser amounts of Prions can be dispersed
through the air and contaminate the water, soil, plantations,
and very large regions. e fourth route is the pathologic
route. Another mechanism of infection that could be very
well explored is the pathogenesis. Prions could be related to
microspheres directed to specic target cells and be embraced
and activated by the endosomes pathway of many types of cells
(Arnoldetal., 1995). Pathogenesis can be divided into natural or
congenital transmission and external transmission. e native or
natural pathogenesis of Prion disease varies including mutation
in human Prion protein gene (PRNP) and external transmitted
causes (Tranulisetal., 2011). Figure2A shows a normal structure
ofPRNP gene (Manson & Tuzi, 2001). Missense mutations and
expansions in the octapeptide region (OR) result in familial
forms of Creutzfeldt-Jakob disease(fCJD) and GSS (Becketal.,
2010; Jansenetal., 2011; Kovácsetal., 2002). On the other hand,
FFI is caused by the D178N mutation, the disease progresses
quickly, and the patient dies within a few months aer the onset
of symptomssleep disorders with agitation, fractionated sleep,
snoring, and daytime sleepiness(Ayuso Blancoetal., 2006;
Montagnaet al., 2003). e inheritablefamilial forms of all
Prion diseases (fCJD, GSS, and FFI) are inherited as autosomal-
dominant disorders (Mastrianni, 2003). e polymorphism
coding for methionine (M) or valine (V) at codon 129 of the
Prion protein gene (PRNP M129V) plays a pivotal role in
the susceptibility to CJD, inuencing familial, transmitted,
and sporadic forms of the disease (Alperovitchetal., 1999),
homozygosity for methionine at position 129 (met/met at codon
129) predisposes susceptibility and earlier age of onset of disease
(Kretzschmar & Illig, 2009; Meadetal., 2009). erefore, the
PRNP polymorphisms isrelatedto specic clinical forms of
Prion diseases, and polymorphism in the regulatory region
of PRNP is associated with increased risk of sporadic CJD
(Sanchez-Juanetal., 2011).
The pathogenesis of external transmission. In theory,
vCJD can be transmitted by ingestion of contaminated
meat derived from cows with BSE.PrPSc may be the major
pathological mechanism to be explored because it survives
the digestion process (Sales, 2006) and is hypothesized to
be amplied by follicular dendritic cells and tingible body
macrophages in gut-associated lymphatic tissue, such as Peyer
patches. PrPSceventually reaches draining lymphatics and
the spleen by migrating to follicular dendritic cells (Aguzzi &
Sigurdson, 2004). Hypothetically, PrPSc reaches the brain via
the sympathetic nervous system from lymphatic tissues, and
PrPScpropagation in the brain causes accumulation resulting
in neurodegeneration (Harris & True, 2006; Aguzzietal.,
2008; Aguzzietal., 2001; Venneti, 2010). us, theoretically,
the conformation of Prions is pH dependent in endosome-like
organelles or lysosomes with acidic environments. Dendritic
cells (DCs) are obvious candidates, but DCs might not account
Food Sci. Technol, Campinas, 34(3): 433-440, July-Sept. 2014 437
Xavier
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huge problem if Prions are not rapidly degraded in the soil by
microorganisms; some studies have demonstrated that the soil
is as possible reservoir of scrapie and CWD agents, which can
persist in the environment for years. Attachment to soil particles
likely inuences the persistence and infectivity of Prions in the
environment (Smithet al., 2011; Gough & Maddison, 2010;
Saundersetal., 2009).
e evidence that soil and other environmental surfaces
can play a role as reservoir of Prions dissemination contributes
to the imminent threat these particles can represent if they
are released into the environment (Maddisonetal., 2010;
Saunderset al., 2011b). Finally, the impact that Prions could
cause to wildlife, especially mammals, is terrifying; people
who had been in contact to contaminated environments or had
ingested inoculated animals could die in days, months, or years.
e long eects of Prion contamination can be terrible
and are similar to radioactive eects. Concluding, it isutmost
importantto alert thescientic community scientic community,
agencies, and governments worldwide to discourage, inhibit,
and investigate those who have this evil intention.
4 Final conclusions
Bioterrorism is as emerging threat that is growing with
the development of biotechnology. e risk of biochemical
weapons falling into wrong hands can be devastating; it could
contaminate cattle, humans and many other animal species
leading to thousands of deaths and would lead to a global
pandemic and economic crisis too.
Acknowledgements
e authors are grateful to Cayman Chemical Company,
Ann Arbor, Michigan. USA.
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... USA Fourth and fifth generation warfare involves biological and economic attacks, if the attacking force has the medicine or the population vaccinated before the attack, it will inflict crippling damage on the enemy force. So, the gain-of-function (GOF) experiments result in an increase in the transmission and pathogenicity of potential pandemic pathogens (PPPs) with the risk of using prions as biochemical weapons for mass destruction, described by Xavie [3]. Humanity for millennia has been waging wars and using its creativity for the most diverse types of weapons. ...
... Therefore, in this article we use the term to refer to a hypothetical virus that contains a protein apparatus capable of inducing the formation of prions terminologically termed as "prion/virus". Furthermore, hypothetically, if a prion/virus were used as a biological weapon, they could damage humans, animals and economy of countries; thus, prion/virus can be a very persuasive object for those who have access to it, as described by Xavie [3]. ...
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... Moreover, there are also novels neurotropic viral strains capable of causing prion diseases [2,3]. Thus, if the attacker has a vaccine these viruses could be used as biological weapons against nations and political enemies [4]. So, we can understand how dynamic the protein world is. ...
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... Though humans solve the majority of their economic, technological and political problems; but emotional disorders, ethical and moral transgressions are still challenging humanity (Sharma et al., 2009). Biotechnology increases the risk of using biochemical weapons for mass destruction (Xavier, 2014). Even a lot of studies reveal the disadvantages of the internet such as social, ethical, and health problems due to its frequent use (Naikoo et al., 2018). ...
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Transgenic mice expressing chimeric prion protein (PrP) genes derived from Syrian hamster (SHa) and mouse (Mo) PrP genes were constructed. One SHa/MoPrP gene, designated MH2M PrP, contains five amino acid substitutions encoded by SHaPrP, while another construct, designated MHM2 PrP, has two substitutions. Transgenic (Tg) (MH2M PrP) mice were susceptible to both Syrian hamster and mouse prions, whereas three lines expressing MHM2 PrP were resistant to Syrian hamster prions. The brains of Tg(MH2M PrP) mice dying of scrapie contained chimeric PrPSc and prions with an artificial host range favoring propagation in mice that express the corresponding chimeric PrP and were also transmissible, at reduced efficiency, to nontransgenic mice and hamsters. Our findings provide genetic evidence for homophilic interactions between PrPSc in the inoculum and PrPC synthesized by the host.