Fwd: SARS Virus Genetically Engineered?

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Thu, 26 Jun 2003 21:12:13 +0100

SARS Virus Genetically Engineered?

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The Institute of Science in Society

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General Enquiries sam

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ISIS Director m.w.ho

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SARS Virus Genetically Engineered?

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The mystery surrounding the SARS virus deepens. Dr. Mae-Wan Ho raises further

questions on whether genetic engineering could have contributed to creating it.

 

Sources for this article are posted on ISIS’ members website.

 

The SARS epidemic

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The SARS epidemic started in the weeks that the ‘allied forces’ were waging war

on Iraq to hunt down Saddam Hussein and his still elusive ‘weapons of mass

destruction’.

 

 

SARS – Severe Acute Respiratory Syndrome – is a completely new infectious

disease spread by human contact. By 20 June 2003, World Health Organisation

figures registered 8461 cases in 31 countries worldwide, and 804 deaths. The

overall death rate is nearly 10% and could be 20% or higher.

 

 

Although there are signs that the disease is under control, there are also fears

that it may return.

 

Mystery of the SARS virus

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The World Health Organisation, which played the key role in coordinating the

research of a dozen laboratories, formally announced on 16 April that a new

pathogen, a member of the coronavirus family never before seen in humans, is the

cause of SARS, though lingering doubt has remained. The virus cannot be

identified all patients diagnosed with SARS, and it can only be isolated from

cultured green monkey kidney cells.

 

 

Known coronaviruses are placed in three groups based on similarities in their

genomes. Group 1 contains the porcine epidemic diarrhoea virus (PEDV), porcine

transmissible gastroenteritis virus (TGEV), canine coronavirus (CCV), feline

infectious peritonitis virus (FIPV) and human coronovirus 229E (HuCV229E); Group

2 contains the avian infectious bronchitis virus (AIBV) and turkey coronavirus;

while Group 3 contains the murine hepatitis virus (MHV) bovine coronavirus

(BCV), human coronavirus (HuOC43) and others.

 

 

The molecular phylogenies published 10 April in the New England Journal of

Medicine, based on small fragments of the polymerase gene, have placed the SARS

virus in a separate group somewhere between groups 2 and 3.

 

 

More detailed analysis, subsequently published in the New England Journal of

Medicine, Science and the Lancet indicate that the new virus is not closely

related to any known virus at all, human, mouse, bovine, cat, pig, bird,

notwithstanding. It is neither a mutant that switched host, nor a recombinant

from existing coronaviruses. It is more complicated than that.

 

SARS virus - a product of genetic engineering?

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Two scientists who have genetic engineered coronaviruses in their laboratories,

Holmes and Enjuanes, suggested in a commentary in the journal Science that the

SARS virus probably “evolved separately from an ancestor of the known

coronavirus, and infected an unidentified animal, bird, or reptile host for a

very long time before infecting humans and starting the SARS epidemic.” (p.1377)

Following soon afterwards, there was a claim that the SARS virus came from the

masked civet cat in south China. But that claim could not be substantiated. An

alternative hypothesis entertained in the mainstream journals was that the virus

came from outerspace.

 

 

There are very unusual features to the SARS virus. Its sequence most closely

matches that of mouse hepatitis virus (MHV) and Bovine corona virus (BCV), both

in group 3. The match is quite good in the middle third of the genome that’s

nearly 30 000nt long, and not good at all for the first third or last third of

the sequence.

 

 

But, antibodies to the SARS virus cross react with FIPV, HuCV229E and TGEV, all

in Group 1. And the SARS virus can grow in Vero green monkey kidney cells, which

no other coronavirus can, with the exception of PEDV, another virus in Group 1.

Could the SARS virus have come from genetic engineering? This is a question that

Ho and Cummins have put to the scientific community. So far, we have not had a

proper reply.

 

 

Holmes and Enjuanes stated in their commentary, “SARS-CoV is also unlikely to

have been created from known coronaviruses by genetic engineering, because at

present it would be impossible to modify 50% of a coronavirus genome without

abrogating viral infectivity.” (p.1377)

 

 

This is a quite a feeble response. The whole point to genetic engineering is

that it greatly increases the scope of recombination, and provides selective

tools to find the most unlikely recombinants that are still infectious.

 

 

Coronaviruses have been subjected to increasing genetic manipulation since the

latter half of the 1990s, when P.S. Masters in Wadworth Center, New York State

Department of Health and New York State University at Albany, used RNA

recombination to introduce extensive changes into the genome of mouse hepatitis

virus (MHV). In a review published in 1999, he wrote, “targeted recombination

could be used to create extensive substitutions to the cornavirus genome,

generating recombinants that could not be made otherwise between two viruses

separated by a species barrier.” (p.254)

 

 

‘Defective interfering RNAs’ – sequences of the viral genome with large

deletions as well as mutations and substitutions or insertions - were used as

donor sequences to introduce major substitutions and point mutations into the

genome of the viruses by RNA recombination.

 

 

In the course of such work, researchers have even isolated a recombinant of

cororanvirus with the green fluorescent protein (GFP) gene, presumably from

cells in which coronaviruses have been cultured, which has become inserted into

the spike protein gene. The GFP gene, originally from a jelly-fish, is

extensively used in genetic engineering as a marker gene because it makes the

cells that have taken up the foreign genes give off a green glow under uv light.

The GFP-coronavirus recombinant could only have come about as an unintended

by-product of genetic engineering.

 

 

In the same review, P.S. Masters showed that both point mutations and large

substitutions can readily be transferred to the last third of the genome of MHV

and other coronaviruses. He further indicated that similar strategies could be

used to mutate and substitute the first third of the genome, though not for the

middle third. “A comprehensive genetic study of the highly complex gene for the

RNA polymerase and all of its associated activities [encoded by the middle third

of the genome] will likely await either the construction of an infectious

full-length clone or the development of an innovative scheme for mutant

selection.” (p.259)

 

 

Is that why the middle third of SARS virus genome has retained good homology to

MHV and BCV, which were the first coronaviruses to be engineered in this manner,

while the other parts are much more different?

 

 

Another feature of the SARS virus is that the spike protein, which determines

host range, is unlike the spike protein of any known coronavirus. Instead, it

appears to have homologies to segments of the human chromosome 7, according to

sequence analysis performed by Howard Urnovitz.

 

 

Urnovitz believes that the spike protein of the SARS virus is the result of

genetic rearrangements provoked by environmental genotoxic agents, much like

those he and his colleagues have detected in Gulf War I veterans suffering from

Gulf War Syndrome.

But how did the virus get to south China? A possible answer was provided by

Urnovitz: Migratory birds that frequent gene-swapping hot spots like southeast

China could have carried the SARS virus there.

Urnovitz himself doesn’t think the SARS virus is the real cause of SARS.

Instead, it is the piece of reshuffled human chromosome 7 that others are

referring to as the spike protein gene of the SARS virus. That alone is

sufficient to trigger serious autoimmune responses in people.

 

 

Hence, to create vaccines against that ‘spike’ protein is also tantamount to

vaccinating people against their own genes (see “Dynamic genomics”, this

series).

 

 

 

 

 

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This article can be found on the I-SIS website at http://www.i-sis.org.uk/

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General Enquiries sam

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