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"protective viruses" - Breakthrough may mean end to flu misery

AlaskaDenise

In Memoriam
Is this real...."protective viruses??"

Breakthrough may mean end to flu misery for millions, says scientist

Chris Benfield
Science and Technology Correspondent

Science may have come up with a way to stop flu.

Warwick University professor Nigel Dimmock has spent 20 years looking for a general antidote to flu viruses and says he is now ready to make one on a large scale.

He is sure it would work against H5N1 ? the new strain of bird flu which has been causing worldwide concern ? and its variants.

And he is ready to start trials on humans, farm chickens and other animals governments and businesses might want to protect.

The university is launching a company in which it and Prof Dimmock have a stake, ViraBiotech, to raise money for trials and preparations for manufacture.

In theory, a human flu-preventer based on the Warwick discoveries could be ready in three years.

It would not wipe out flu viruses, but it could stop the epidemics which disrupt economies and cost lives when a virus mutates and spreads suddenly.

It could also prevent run-of-the-mill misery and cost arising from the 144 viruses already established in humans and animals such as pigs, poultry and horses.

Prof Dimmock's method promises to work against all viruses in the Influenza A category ? the family which causes most trouble ? and it might also work against some Influenza B.

It involves "protective viruses" ? incomplete imitations of a full flu virus, which occur naturally along with the viruses they mimic.

Nobody knows what they are for, in evolutionary terms, but one theory is that, by competing for resources, they stop the damaging virus from killing its host too quickly.

Prof Dimmock, 66, is an expert on what happens when a protective virus gets into a host before the real thing.

On its own, it cannot reproduce, because there is a bit missing from one of its strands of RNA, the genetic material which carries the codes for building cells.

When a real virus arrives, they team up and both reproduce, but the dummy virus works faster, because it is smaller. It swamps the "nasty" version, so the body can develop antibodies before damage is done.

Prof Dimmock has seen the process in laboratory cultures, mice and ferrets.

A dose is effective for six weeks and should cost no more than existing vaccines and anti-viral drugs.

He now has a protective virus from the Influenza A family which he can reproduce consistently and check for quality. But he stresses that genetic modification is not involved.

"It is a naturally occurring product," he said yesterday.

The system could lead to similar medicines against colds, hepatitis and other viral illnesses.

An independent expert, John Oxford, head of virology at three London hospitals, said the idea had "huge potential".

04 October 2006

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Scientists say they are developing an entirely new way of providing instant protectio

Scientists say they are developing an entirely new way of providing instant protectio

<TABLE cellSpacing=0 cellPadding=0 width=416 border=0><TBODY><TR><TD width=213> E-mail this to a friend </TD><TD width=203> Printable version </TD></TR></TBODY></TABLE><TABLE cellSpacing=0 cellPadding=0 width=629 border=0><TBODY><TR><TD colSpan=3>Treatment 'to neutralise all flu'

</TD></TR><TR><TD vAlign=top width=416><!-- S BO --><!-- S IIMA --><TABLE cellSpacing=0 cellPadding=0 width=203 align=right border=0><TBODY><TR><TD>
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There are fears of flu pandemic

</TD></TR></TBODY></TABLE><!-- E IIMA --><!-- S SF -->Scientists say they are developing an entirely new way of providing instant protection against flu.
In preliminary tests, it was found to protect animals against various strains of the virus - and may also protect against future pandemic strains.
University of Warwick researchers used a flu virus naturally stripped of some genetic material to compete with other invading flu viruses.
This slowed the rate of infection so much the body could fight it off. <!-- E SF -->
In effect, the invading virus became its own vaccine by triggering an immune response sufficiently powerful to neutralise it before it could gain a strong enough foothold.
The Warwick team plan to develop the treatment as a nasal spray.
Experts warned much more testing was required.
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This is cutting edge science, but there is a lot that could still go wrong
end_quote_rb.gif



Professor John Oxford

</TD></TR></TBODY></TABLE><!-- E IBOX -->
However, they said the development of the vaccine was timely, amid concerns the H5N1 bird flu strain circulating in south east Asia could mutate into a pandemic strain which would put millions of lives at risk.
Existing vaccination methods depend on stimulating the body's immune system, so that white blood cells produce antibodies that attach to the surface of the virus and start the process of killing it.
This works well for many diseases, such as smallpox, polio and measles, but is much less effective with flu, as the coat of the flu virus is continually changing.
Vaccination against one strain of flu is totally ineffective against another.
Crowded out
Professor Nigel Dimmock has spent more than two decades developing the new approach.
The "protecting virus" with which he worked had naturally lost around 80% of the genetic material of one of its eight RNA constituent segments. This deletion makes the virus harmless and prevents it from reproducing by itself within a cell, so that it cannot spread like a normal influenza virus.
However, if it is joined in the cell by another influenza virus, it retains its harmless nature but starts to reproduce - and at a much faster rate than the new influenza virus.
This fast reproduction rate - spurred by the new flu infection - means that the new invading influenza is effectively crowded out.
This vastly slows the progress of the new infection, prevents flu symptoms, and gives the body time to develop an immune response to the harmful new invader.
One size fits all
The Warwick team believes its research indicates the protecting virus would have the same effect regardless of the strain of flu infection.
This is because the coat of the virus is irrelevant to the protection process - the effect works on the virus genes inside the cell.
In addition it protects instantly, whereas protection generated by conventional flu vaccination takes two to three weeks to become fully effective.
Experiments so far show that a single dose of protecting virus can be given six weeks before, and 24 hours after an infection with flu virus and be effective.
The Warwick research team has now filed a patent on the protecting virus and is exploring ways of taking it through human clinical trials and testing on birds.
Professor John Oxford, a virologist at Queen Mary College School of Medicine, London, said: "This is cutting edge science, but there is a lot that could still go wrong. "To have something that could more or less guarantee coverage against anything that this virus could throw at us would be absolutely spot on."<!-- E BO -->

</TD></TR></TBODY></TABLE>
http://news.bbc.co.uk/1/hi/health/5404184.stm
 
Re: "protective viruses" - Breakthrough may mean end to flu misery

This sounds similar to how "cross reactive immunity" with standard flu VAX works. It must be given <30 days prior to exposure.

It sounds the the "backfire" of the viral world. :D

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Re: "protective viruses" - Breakthrough may mean end to flu misery

Does anybody have any harder information, perhaps a scientific paper?

Based on the information in the article this sounds a dangerous proposition. Allowing a flu virus to replicate in a cell with additional genetic material from another virus would, on the face of it, give it an opportunity to acquire new genetic sequences through recombination; with unpredictable results. However if it reduces the infection rate perhaps this is an acceptable risk.
 
Re: "protective viruses" - Breakthrough may mean end to flu misery

JJackson said:
Does anybody have any harder information, perhaps a scientific paper?

Based on the information in the article this sounds a dangerous proposition. Allowing a flu virus to replicate in a cell with additional genetic material from another virus would, on the face of it, give it an opportunity to acquire new genetic sequences through recombination; with unpredictable results. However if it reduces the infection rate perhaps this is an acceptable risk.

Sounds like defective intefering particles, which have been known for decades and are made naturally (sequences from WSN/33 are at Genbank).
 
Re: "protective viruses" - Breakthrough may mean end to flu misery

<TABLE class=resultstable cellSpacing=0 cellPadding=4 width="100%" border=0><TBODY><TR bgColor=white><TD align=left><INPUT onclick=setAll(this.checked) type=checkbox value=1984 name=checkbox> </TD><TD class=displaytablerow align=left></TD><TD>D10572 </TD><TD>A/WSN/33 (recomb) (DI-1) </TD><TD>PA (3) </TD><TD>438 </TD><TD>1933 </TD><TD>H1N1 </TD><TD></TD></TR><TR bgColor=#a7c4ef><TD align=left><INPUT onclick=setAll(this.checked) type=checkbox value=1986 name=checkbox> </TD><TD class=displaytablerow align=left></TD><TD>D10573 </TD><TD>A/WSN/33 (recomb) (DI-2) </TD><TD>PA (3) </TD><TD>432 </TD><TD>1933 </TD><TD>H1N1 </TD><TD></TD></TR><TR bgColor=white><TD align=left><INPUT onclick=setAll(this.checked) type=checkbox value=1988 name=checkbox> </TD><TD class=displaytablerow align=left></TD><TD>D10574 </TD><TD>A/WSN/33 (recomb) (DI-3) </TD><TD>PA (3) </TD><TD>400 </TD><TD>1933 </TD><TD>H1N1 </TD></TR></TBODY></TABLE>
 
Re: "protective viruses" - Breakthrough may mean end to flu misery

This is not "protective viruses", however it shows how the H9N2 protects....
http://jvi.asm.org/cgi/content/full/76/10/4886

Protective Cross-Reactive Cellular Immunity to Lethal A/Goose/Guangdong/1/96-Like H5N1 Influenza Virus Is Correlated with the Proportion of Pulmonary CD8<SUP>+</SUP> T Cells Expressing Gamma Interferon

Sang Heui Seo,<SUP>1</SUP> Malik Peiris,<SUP>2</SUP> and Robert G. Webster<SUP>1</SUP><SUP>*</SUP>


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RESULTS
Cross-reactive protection. Only the HA genes of the currently circulating A/Goose/Guangdong/1/96-like<SUP> </SUP>H5N1 viruses are similar to those of the H5N1/97 viruses (29).<SUP> </SUP>To determine whether immunity to the currently circulating H9N2<SUP> </SUP>influenza viruses cross-protects chickens from the highly pathogenic<SUP> </SUP>H5N1 influenza viruses, we immunized chickens with A/Duck/Y280-like<SUP> </SUP>A/Chicken/HK/SF3/99 (H9N2) virus 20 to 100 days before challenge<SUP> </SUP>with A/Goose/Guangdong/1/96-like A/Goose/HK/437-4/99 (H5N1).<SUP> </SUP>All nonimmunized chickens began to show clinical signs of illness<SUP> </SUP>(reddened combs, dyspnea, dropping heads, and difficulty standing)<SUP> </SUP>2 or 3 days after challenge. Four of ten control chickens died<SUP> </SUP>(Table 1); the rest recovered within 5 days after infection<SUP> </SUP>but lost up to 20% of their body weight (data not shown). Chickens<SUP> </SUP>immunized with A/Chicken/HK/SF3/99 (H9N2) virus 20 and 30 days<SUP> </SUP>before challenge showed no clinical signs of illness, but signs<SUP> </SUP>of illness were seen in chickens immunized 60 days before challenge<SUP> </SUP>(Table 1). Two of 10 chickens immunized 60 days in advance showed<SUP> </SUP>signs of illness that began 3 days after challenge and recovered<SUP> </SUP>by day 5 after challenge. Seven of 10 chickens immunized 100<SUP> </SUP>days before challenge showed clinical signs of illness, and<SUP> </SUP>two of these died. These findings showed that the protective<SUP> </SUP>immunity declined over time. Chicken immunized 20 days earlier<SUP> </SUP>with P/Chicken/HK/QB4/99(Newcastle disease virus) and challenged<SUP> </SUP>with A/Goose/Guangdong/1/96-like A/Goose/HK/437-4/99 (H5N1)<SUP> </SUP>showed 75% mortality (data not shown).<SUP> </SUP>
<!-- null -->
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.(end of DISCUSSION)
Cross-reactive cellular immunity seems to have two important<SUP> </SUP>potential consequences: the protection of hosts from disease<SUP> </SUP>and the perpetuation of viruses in these hosts. Some protected<SUP> </SUP>chickens shed H5N1 viruses in their tracheae and cloacae. H9N2<SUP> </SUP>viruses similar to A/Chicken/HK/SF3/99 are endemic in chickens<SUP> </SUP>in southeastern China (18), and while this prior immunity may<SUP> </SUP>mask the pathogenicity of subsequent H5N1 infections, it does<SUP> </SUP>not completely suppress infection. Replication of H5N1 virus<SUP> </SUP>in H9N2-immunized chickens may provide an opportunity for reassortment<SUP> </SUP>between A/Goose/Guangdong/1/96-like viruses and other endemic<SUP> </SUP>avian viruses in the Hong Kong bird markets, thus increasing<SUP> </SUP>the odds that more virulent H5N1 viruses will emerge. The outbreaks<SUP> </SUP>of H5N1 viruses in Hong Kong poultry markets in 2001 support<SUP> </SUP>this premise. The isolates from these outbreaks are reported<SUP> </SUP>to be multiple reassortant viruses between A/Goose/Guangdong/1/96-like<SUP> </SUP>H5N1 viruses and other avian viruses endemic to southeastern<SUP> </SUP>Asia (personal communication with Y. Guan). We are now conducting<SUP> </SUP>a study of cross-reactive protection against H5N1 influenza<SUP> </SUP>viruses isolated from poultry during outbreaks in Hong Kong<SUP> </SUP>in 2001. In conclusion, our findings demonstrate that memory<SUP> </SUP>CD8<SUP>+</SUP> T cells and TCR
agr.gif
/? T cells primed by exposure<SUP> </SUP>to H9N2 influenza virus are key elements in cross-reactive immune<SUP> </SUP>control of the highly pathogenic H5N1 influenza virus in chickens<SUP> </SUP>and that protective immunity is correlated with the percentage<SUP> </SUP>of memory CD8<SUP>+</SUP> T cells expressing IFN-
ggr.gif
in the lungs.<SUP> </SUP>
 
Re: "protective viruses" - Breakthrough may mean end to flu misery

<DT><TABLE cellSpacing=0 cellPadding=0 width="100%"><TBODY><TR><TD><INPUT type=checkbox value=2238471 name=uid>1: Virology. 1990 Dec;179(2):821-6.</TD><TD align=right>Related Articles,<SCRIPT language=JavaScript1.2><!--var PopUpMenu2_LocalConfig_jsmenu3Config = [ ["ShowCloseIcon","yes"], ["Help","window.open('/entrez/query/static/popup.html','Links_Help','resizable=no,scrollbars=yes,toolbar=no,location=no,directories=no,status=no,menubar=no,copyhistory=no,alwaysRaised=no,depend=no,width=400,height=500');"], ["TitleText"," Links "]]var jsmenu3Config = [ ["UseLocalConfig","jsmenu3Config","",""]]//--></SCRIPT><SCRIPT language=JavaScript1.2><!--var Menu2238471 = [ ["UseLocalConfig","jsmenu3Config","",""], ["Cited in PMC","window.top.location='http://www.pubmedcentral.gov/tocrender.fcgi?action=cited&tool=pubmed&pubmedid=2238471'","",""], ["Books","window.top.location='http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?itool=pubmed_Citation&cmd=Retrieve&db=pubmed&list_uids=2238471&dopt=Books'","",""], ["LinkOut","window.top.location='http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?itool=pubmed_Citation&cmd=Retrieve&db=pubmed&list_uids=2238471&dopt=ExternalLink'","",""]]//--></SCRIPT> Links </TD></TR></TBODY></TABLE></DT><DD>
Defective interfering particles: effects in modulating virus growth and persistence.

Bangham CR, Kirkwood TB.

Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, United Kingdom.

Defective interfering virus particles (DIP) frequently play an important part in viral persistence in vitro, and may in some instances modify a virus infection in vivo, causing attenuation or persistence of the infection. To explain certain aspects of the growth of these mutants in vitro, other factors have been invoked such as interferon, mutations in the wild-type virus or the infected cells, or other substances released by infected cells that attenuate the infection. We present here a simple model of the growth of DIP in vitro which shows that (a) the observed population dynamics of DIP can readily be explained without invoking such extrinsic factors; (b) the initial multiplicity of infection of DIP is the principal determinant of the outcome of infection in both single- and repeated-passage cultures; and (c) in a long-term culture in vitro, the criterion used to decide the time of virus passage directly determines how long the standard virus, DIP, and cells survive. This model may be used with minor modifications to predict the behavior in vitro of other mutant viruses with a dominantly interfering phenotype.
<DD><DD>.

</DD>
 
Re: "protective viruses" - Breakthrough may mean end to flu misery

A question for Dr. Niman please, if you can help - why would this modified influenza virus reproduce faithfully when others do not (and therefore remain harmless), and if it only has one area of deletion on one of its eight genes, would it not be vulnerable to recombination or reacquisition of the missing material? Or wouldn't this matter? This research would also imply to me that the researchers have identified which section of the influenza gene - or one of the 8 strands - is responsible for virulence, but I thought we were not clear on which aspects of the genetic strucutre are responsible for this, and that the issue was multi factorial and virulence factors could be found in multiple different places across the 8 RNA segments.

Many thanks for your opinion.
 
Re: "protective viruses" - Breakthrough may mean end to flu misery

The description is scetchy, so let me guess:
these protective viruses somehow manage to steal some
genetic material from the invading viruses and can build it
into their own genetic code.
Then they can reproduce themselves, invade and destroy cells,
so these cells are no longer available for the invaders.
But they are still destroyed.
Now, the protective virus somehow dies before it can do too
much damage, so I assume it is not able to travel within
the body large distances so only the cells in some
small area are destroyed.
But now the invader-virus has no intact cells available in its reach
and it starts to travel restlessly in the body until it finally finds
an intact cell to infect. But by that time the immune system
has already taken the defence positions.
Doesn't sound very good to me.

But when it actually works in mice, that's good news, of course.
 
Re: "protective viruses" - Breakthrough may mean end to flu misery

Since this process works by "crowding out the competition", I wonder if part of this process was involved in the 1957 H2N2 causing the 1918 H1N1 to "disappear" from circulation, then the later 1968 H3N2 replaced H2N2?

If this is part of the replacement equation, will H5N1 cause currently-circulating influenzas to disappear?

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