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-------- Original Message --------
| Subject:
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Re: PRO/AH/EDR> Ebola-Reston, porcine -
Philippines (06), FAO/OIE/WHO |
| Date:
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Sat, 27 Dec 2008 11:14:05 -0800 |
| From:
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"Stephen M. Apatow"
<s.m.apatow@pathobiologics.org> |
| To:
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ivphc_wg@pathobiologics.org |
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[ProMED-mail's request for information on any known additional attempts
to screen for filoviruses in porcine tissues, particularly from
PRRS-affected tropical/subtropical countries, either by the PIADC lab
or by others/elsewhere, is hereby repeated. - Mod.AS] -
Dear
Colleagues:
In the context of filoviruses in porcine research:
Here we defined the
main
viral determinant of Ebola virus pathogenicity; synthesis of the virion
glycoprotein (GP) of Ebola virus Zaire induced cytotoxic effects in
human
endothelial cells in vitro and in vivo. This effect mapped to a
serine−threonine-rich,
mucin-like domain of this type I transmembrane glycoprotein, one of
seven
gene products of the virus. Gene transfer of GP into explanted
human
or porcine blood vessels caused massive endothelial cell loss within 48
hours that led to a substantial increase in vascular permeability.
Deletion
of the mucin-like region of GP abolished these effects without
affecting
protein expression or function. GP derived from the Reston strain of
virus,
which causes disease in nonhuman primates but not in man, did not
disrupt
the vasculature of human blood vessels. In contrast, the Zaire GP
induced
endothelial cell disruption and cytotoxicity in both nonhuman primate
and
human blood vessels, and the mucin domain was required for this effect.
These findings indicate that GP, through its mucin domain, is the viral
determinant of Ebola pathogenicity and likely contributes to hemorrhage
during infection. -- Identification of the Ebola virus glycoprotein as the
main viral determinant of vascular cell cytotoxicity and injury, Nature Medicine 6, 886 -
889
(2000) doi:10.1038/78654.
Pathogenicity and variables associated with reassortment, protein
expression and/or function of
virion
glycoprotein (GP):
For non-segmented negative-sense RNA virus, more
and
more evidences of homologous recombination were found. Most interesting
example lies in Zaire Ebola Virus, recombinant sequences form a
distinct
circulating lineage, with readily identifiable parents, that is
transmitted
among multiple individuals in a population (8). This recombination
event
took place between 1996 and 2001 and gave rise to a group of
recombinant
viruses that were responsible for a series of outbreaks in 2001–2003. The
potential for recombination adds an additional level of complexity to
unraveling
and potentially controlling the emergence of ZEBOV in humans and
wildlife
species. -- Homologous recombination in negative-sense RNA
viruses: on
evolutionary aspects, Guan-Zhu Han, College of Life Science,
Shandong Normal University, Jinan, Shandong 250014, China.
As noted in "Ebola and Marburg Viruses" (Hans-Dieter
Klenk, Heinz Feldmann. Online Book Preview), The requirement of
biosafety level 4 containment has greatly hampered filovirus research.
To circumvent the need for a high level of biohazard containment, some
investigators have pseudotyped vesicular stomatitis virus (VSV) or
murine leukemia Virus (MLV) with filoviral glycoproteins.
Studies analyzing Ebola virus replication have been
severely
hampered by the extreme pathogenicity of this virus. To permit analysis
of the host range and function of the Ebola virus glycoprotein (Ebo-GP),
we have developed a system for pseudotyping these glycoproteins into
murine leukemia virus (MLV). This pseudotyped virus, MLV(Ebola), can
be readily concentrated to titers which exceed 5 × 106
infectious units/ml and is effectively neutralized by antibodies specific
for Ebo-GP. Analysis of MLV(Ebola) infection revealed that
the host range conferred by Ebo-GP is very broad, extending to
cells of a variety of species. Notably, all lymphoid cell lines
tested were completely resistant to infection; we
speculate
that this is due to the absence of a cellular receptor for
Ebo-GP
on B and T cells. The generation of high-titer MLV(Ebola)
pseudotypes will be useful for the analysis of immune
responses to
Ebola virus infection, development of neutralizing
antibodies,
analysis of glycoprotein function, and isolation of the
cellular
receptor(s) for the Ebola virus. -- Characterization
of Ebola Virus Entry by Using Pseudotyped Viruses: Identification of
Receptor-Deficient
Cell Lines, J Virol, April 1998, p.
3155-3160, Vol.
72, No. 4.
As per the importance asymptomatic infection and Peter Roeder's
note
(PRO/AH> Ebola-Reston, porcine - Philippines (05)):
When I was working at the Philippines Animal Health
Centre
in the early 1990s, I remember discussing the Ebola-Reston issue with
Filipino
colleagues in the Bureau of Animal Industry who were involved in trying
to
understand what had happened..... Therefore, it seemed to me at the
time
that it was possible that the Ebola-Reston virus could conceivably have
come
from Africa, not necessarily from the Philippines, and infected
Philippine
monkeys there. One has to wonder if the virus could have moved from
there
into indigenous species capable of constituting a reservoir (e.g.,
shrews,
rodents, bats) and from there infecting swine, both indigenous and
domesticated.
African swine fever (ASF) is an asymptomatic
infection
of warthogs and bushpigs, which has become an emergent disease of
domestic pigs characterized by hemorrhage, lymphopenia, and
disseminated
intravascular coagulation.... -- African Swine Fever Virus
Infection
of Porcine Aortic Endothelial Cells Leads to Inhibition of Inflammatory
Responses,
Activation of the Thrombotic State, and Apoptosis: Journal of
Virology,
November 2001, p. 10372-10382, Vol. 75, No. 21. Full Text.
In the context of asymptomatic Ebola-Reston in domesticated pigs,
surveillance can only be accomplished through access to molecular
diagnostic technologies, genomic analysis and collaborative guidance
for containment and control.
The Pandemic Model
H5N1 has spread across the globe as a containable animal health
pandemic, with human exposure proportional to direct environmental
contact of impoverished populations (3.5 billion + with no public
health infrastructure). Since we
did not view large numbers of human deaths following exposure, the
extreme
distortion of statistical information associated with human infection
and
geographical impact appears to be a direct result of restricted access
to
molecular diagnostic technologies:
While just 390 people have been infected since 2003 and
246
have died, experts fear H5N1 could acquire the ability to spread easily
from human to human, setting off a pandemic that could kill hundreds of
millions
of people. -- Health, emergency staff get drugs first in pandemic,
Reuters, 17 December 2008.
Could we have missed the progression of a pandemic that has already
impacted populations across the globe, because the clinical
manifestation of infection was mild?
The global public health discussion "PRO/AH> Avian influenza, human (140): atypical
infections" (ProMED: 20060905.2522: 05-SEP-2006) presents variables
excluded in the current H5N1 pandemic discussion:
- Atypical
H5N1 infections (encephalitis, diarrheal, gastrointestinal
illness)
were excluded from the potential clinical spectrum of challenge.
- While
much has been made of the fulminant cases of presumed viral pneumonia
in
1918, Dr. Brundage's research indicates that the majority of pneumonia
cases, even in 1918, were either secondary bacterial pneumonias
following an influenza infection or mixed viral and bacterial
pneumonias. In the
pre-antibiotic era, these cases of bacterial pneumonia carried a very
high
mortality rate; however, with appropriate antibiotic therapy, many
such
patients may be saved.
The
antibiotic
variable, does contrast with the global marketing strategy of antiviral
drugs
(that D.A. Henderson said would be worthless in early discussions),
that
have now yeilded widespread drug resistance due to their misuse. See:
Oseltamivir Resistance — Disabling Our Influenza
Defenses: NEJM, Volume 353:2633-2636, December
22, 2005, Number 25.
Ebola-Reston, porcine - Philippines is our new wake up
call for access to molecular diagnostic technologies that can reach the
grassroots level
in every UN member country. A similar strategic focus in United
States
is a reference point for the international community (U.S. Agricultural and Food Security, Breeze, Horn).
Looking forward to solution oriented feedback as we advance the global One Health
initiative to the next level.
Related:
- The Future of Biodetection Systems - Final Workshop
Analysis: The Future of Biodetection Systems Workshop was held
last year to bring together industry, academia, national labs, and
federal agency personnel in an interactive process, to develop a
roadmap for research and development investment in
biodetection. Sponsored by Los Alamos National
Laboratory,September 26 & 27 2006. -- Overview: BTACC Pathobiologics International.
Keynote: DNA-based Detection Technologies (Powerpoint):
Stephen M.Apatow, Humanitarian University Consortium Graduate
Studies Center forMedicine,
Veterinary Medicine and Law.
- International Law, Communicable Diseases and the
Geopolitical Objective of Minimal Interference with World Trade and
Travel: Stephen M. Apatow, Humanitarian Resource Institute Legal
Resource Center, 5 May 2003.
Stephen M. Apatow
Founder, Director of Research & Development
Humanitarian Resource Institute
Humanitarian University Consortium Graduate Studies
Center for Medicine, Veterinary Medicine & Law
Phone: 203-668-0282
Email: s.m.apatow@humanitarian.net
Internet: www.humanitarian.net
Pathobiologics International
Internet: www.pathobiologics.org
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