New evidence of cytokine storm in avian flu cases

[Mingus]

They talk about that study
http://www.h5n1experts.org/forum/sho...ion+chemokines

In 1997, avian influenza virus H5N1 was transmitted directly from chicken to human and resulted in a severe disease that had a higher mortality rate in adults than in children. The characteristic mononuclear leukocyte infiltration in the lung and the high inflammatory response in H5N1 infection prompted us to compare the chemokine responses between influenza virus-infected adult and neonatal monocyte-derived macrophages (MDMs). The effects of avian influenza virus A/Hong Kong/483/97 (H5N1) (H5N1/97), its precursor A/Quail/Hong Kong/G1/97 (H9N2) (H9N2/G1), and human influenza virus A/Hong Kong/54/98 (H1N1) (H1N1/98) were compared. Significantly higher expression of CCL2, CCL3, CCL5, and CXCL10 was induced by avian influenza viruses than by human influenza virus. Moreover, the increase in CCL3 expression in H5N1/97-infected adult MDMs was significantly higher than that in neonatal MDMs. Enhanced expression of CCR1 and CCR5 was found in avian virus-infected adult MDMs. The strong induction of chemokines and their receptors by avian influenza viruses, particularly in adult MDMs, may account for the severity of H5N1 disease.

Laymen,s term:

Chemokine or cytokine or interleukine are more stimulated by avian virus.
H5N1 stimulate them more than others avian virus.
They stimulate more adult cells than young cells.

This may be the cause of H5N1 severity.

[AlaskaDenise]

Re: New evidence of cytokine storm in avian flu cases

By a "stronger response" - do they mean a simple count or a ratio to size? If it's a simple cell count, that's what I would expect a body to produce for a neonatal case.

Were all adult responses the same, or did they decrease for older folks, as some charts have shown?

.

[Snowy Owl]

Re: New evidence of cytokine storm in avian flu cases

I am on a Trail concerning this, I still wait for some responses.

Maybe some of us can find the link with neurology.

If some of our Members or Visitors have some background in Neurology and its relation as a catalyst it would be helpfull.

[hawkeye]

Re: New evidence of cytokine storm in avian flu cases

Bird flu virus found in blood of human victims
ETHAN MCNERN

THE H5N1 bird flu virus replicates far more aggressively in people than common human flu viruses

A study of patients in Vietnam also found the virus in the blood stream of many of the human victims, which means it may have spread to other parts of the body, it was reported in Nature Medicine.

Menno de Jong, a key researcher in the study, said the unusually high viral loads triggered intense "cytokine" responses - an immune system overreaction that can be fatal. Cytokines are proteins that fight off intruders such as bacteria and viruses.

"During H5N1 infection, the [cytokine] response seems to be very, very intense. Cytokines want to get rid of this intruder, but if you have very high levels of cytokines, it can also damage the body," Mr de Jong said.

The study involved 18 people infected with H5N1 and eight with human flu in 2004 and 2005 in Vietnam. Scientists found far higher viral loads in the nose and throats of those infected with bird flu than human flu.

Thirteen of those infected with H5N1 died and the virus was found in the blood of at least nine of them. The virus was also found in the rectums of most of those with H5N1, suggesting it could have spread through the blood stream into the gastrointestinal tract. Those with common flu had no virus in their blood or rectum. No-one died in that group.

"The fatal outcome of H5N1 infections seems to be associated with high levels of replication of the virus and also the detection of the virus in the blood," said Mr de Jong, of the Oxford University Clinical Research Unit at the Hospital for Tropical Diseases in Ho Chi Minh City in southern Vietnam.

The team was able to draw a connection between those who were most ill and the level of cytokines found in them. "We found that levels of cytokines were much higher in H5N1 patients than in the human flu cases. Again, the highest levels of cytokines were found in those who died of H5N1," he said.

[AlaskaDenise]

Re: New evidence of cytokine storm in avian flu cases

Both these studies don't discuss the idea that the cytokine load might be high because the body continues to "up the level" when prior elimination attempts fail due to NS1 mutation.

Put that same NS1 mutation into ordinary flu and voila - cytokine storms as in H5N1. See http://vir.sgmjournals.org/cgi/content/full/86/4/1121 The reverse is true also - "when NS1 is absent or altered, the virulence<SUP> </SUP>of influenza A viruses is highly attenuated. " However the results are not consistant.

I still haven't found an answer as to why the levels of IL-10 (anti-inflammatory cytokine) don't always match the elevated levels of inflammatory cytokines. Different test have different results.

.

[AlaskaDenise]

Re: New evidence of cytokine storm in avian flu cases

Implications of virus-containing blood.....

....the virus in the blood stream of many of the human victims, which means it may have spread to other parts of the body,

So we've gone from virus-containing blood in one boy to many victims!
This has implications for not only high pathogenicity, but also blood transfusions (as discussed earlier).

I'm also haunted by a discussion months ago regarding the characteristics of this virus to meet the primary goal of all virus - to persist. I cannot find the original discussion (please supply if known), but it was speculated that this virus did not need keep it's host alive to persist, due to characteristics that allowed it to spread, whether or not it's host died. I believe virus in the blood was one of those characteristics.

Does newer data support that possibility? Perhaps the many H5N1 unknowns mean that we should bury this idea.
.

[HenryN]

Re: New evidence of cytokine storm in avian flu cases

The level of H5N1 is dictated by changes in PB2. Most of the patients had E627K. Three of the four that didn't had D710N. E627K increases virus production 20X (and is most efficient at 34 C - temperature inside a human nose in the winter). D710N increases virus production 3-4X.

The amount of H5N1 triggers the immune response. Although all patients with E627K did not die, E627K is an ALL human flu isolates (H1N1, H3N2, H2N2, H1N2, and 1918 pandemic H1N1) and is a major factor in most H5N1 infections of mammals (humans, pigs, tigers, domestic cats, dogs, stone martins, foxes, etc).

[HenryN]

Re: New evidence of cytokine storm in avian flu cases

Here's the swine list of E627K going from the corn fields in Iowa in 1930 to Ontario, Canada in 2004

<TABLE class=resultstable cellSpacing=0 cellPadding=4 width="100%" border=0><TBODY><TR bgColor=#a7c4ef><TD align=left><INPUT onclick=setAll(this.checked) type=checkbox value=137974 name=checkbox> </TD><TD class=displaytablerow align=left></TD><TD>DQ280245 </TD><TD>A/swine/Ontario/11112/04 </TD><TD>PB2 (1) </TD><TD>2280 </TD><TD>2004 </TD><TD>H1N1 </TD><TD></TD></TR><TR bgColor=white><TD align=left><INPUT onclick=setAll(this.checked) type=checkbox value=137966 name=checkbox> </TD><TD class=displaytablerow align=left></TD><TD>DQ280237 </TD><TD>A/swine/Ontario/23866/04 </TD><TD>PB2 (1) </TD><TD>2280 </TD><TD>2004 </TD><TD>H1N1 </TD><TD></TD></TR><TR bgColor=#a7c4ef><TD align=left><INPUT onclick=setAll(this.checked) type=checkbox value=137958 name=checkbox> </TD><TD class=displaytablerow align=left></TD><TD>DQ280229 </TD><TD>A/swine/Ontario/48235/04 </TD><TD>PB2 (1) </TD><TD>2339 </TD><TD>2004 </TD><TD>H1N2 </TD><TD></TD></TR><TR bgColor=white><TD align=left><INPUT onclick=setAll(this.checked) type=checkbox value=137934 name=checkbox> </TD><TD class=displaytablerow align=left></TD><TD>DQ280205 </TD><TD>A/swine/Ontario/55383/04 </TD><TD>PB2 (1) </TD><TD>2280 </TD><TD>2004 </TD><TD>H1N2 </TD><TD></TD></TR><TR bgColor=#a7c4ef><TD align=left><INPUT onclick=setAll(this.checked) type=checkbox value=127292 name=checkbox> </TD><TD class=displaytablerow align=left></TD><TD>DQ139325 </TD><TD>A/swine/Zhejiang/1/2004 </TD><TD>PB2 (1) </TD><TD>2341 </TD><TD>2004 </TD><TD>H1N2 </TD><TD></TD></TR><TR bgColor=white><TD align=left><INPUT onclick=setAll(this.checked) type=checkbox value=137926 name=checkbox> </TD><TD class=displaytablerow align=left></TD><TD>DQ280197 </TD><TD>A/swine/Alberta/56626/03 </TD><TD>PB2 (1) </TD><TD>2282 </TD><TD>2003 </TD><TD>H1N1 </TD><TD></TD></TR><TR bgColor=#a7c4ef><TD align=left><INPUT onclick=setAll(this.checked) type=checkbox value=137950 name=checkbox> </TD><TD class=displaytablerow align=left></TD><TD>DQ280221 </TD><TD>A/swine/Ontario/52156/03 </TD><TD>PB2 (1) </TD><TD>2280 </TD><TD>2003 </TD><TD>H1N2 </TD><TD></TD></TR><TR bgColor=white><TD align=left><INPUT onclick=setAll(this.checked) type=checkbox value=137918 name=checkbox> </TD><TD class=displaytablerow align=left></TD><TD>DQ280189 </TD><TD>A/swine/Ontario/57561/03 </TD><TD>PB2 (1) </TD><TD>2280 </TD><TD>2003 </TD><TD>H1N1 </TD><TD></TD></TR><TR bgColor=#a7c4ef><TD align=left><INPUT onclick=setAll(this.checked) type=checkbox value=69449 name=checkbox> </TD><TD class=displaytablerow align=left></TD><TD>AY363463 </TD><TD>A/swine/Hong Kong/1212/02 </TD><TD>PB2 (1) </TD><TD>1228 </TD><TD>2002 </TD><TD>H3N2 </TD><TD></TD></TR><TR bgColor=white><TD align=left><INPUT onclick=setAll(this.checked) type=checkbox value=69448 name=checkbox> </TD><TD class=displaytablerow align=left></TD><TD>AY363462 </TD><TD>A/swine/Hong Kong/411/02 </TD><TD>PB2 (1) </TD><TD>1193 </TD><TD>2002 </TD><TD>H3N2 </TD><TD></TD></TR><TR bgColor=#a7c4ef><TD align=left><INPUT onclick=setAll(this.checked) type=checkbox value=69447 name=checkbox> </TD><TD class=displaytablerow align=left></TD><TD>AY363461 </TD><TD>A/swine/Hong Kong/74/02 </TD><TD>PB2 (1) </TD><TD>1193 </TD><TD>2002 </TD><TD>H3N2 </TD><TD></TD></TR><TR bgColor=white><TD align=left><INPUT onclick=setAll(this.checked) type=checkbox value=69445 name=checkbox> </TD><TD class=displaytablerow align=left></TD><TD>AY363459 </TD><TD>A/swine/Hong Kong/1311/01 </TD><TD>PB2 (1) </TD><TD>1226 </TD><TD>2001 </TD><TD>H3N2 </TD><TD></TD></TR><TR bgColor=#a7c4ef><TD align=left><INPUT onclick=setAll(this.checked) type=checkbox value=69444 name=checkbox> </TD><TD class=displaytablerow align=left></TD><TD>AY363458 </TD><TD>A/swine/Hong Kong/9285/01 </TD><TD>PB2 (1) </TD><TD>1235 </TD><TD>2001 </TD><TD>H3N2 </TD><TD></TD></TR><TR bgColor=white><TD align=left><INPUT onclick=setAll(this.checked) type=checkbox value=69446 name=checkbox> </TD><TD class=displaytablerow align=left></TD><TD>AY363460 </TD><TD>A/swine/Hong Kong/9840/01 </TD><TD>PB2 (1) </TD><TD>1212 </TD><TD>2001 </TD><TD>H3N2 </TD><TD></TD></TR><TR bgColor=#a7c4ef><TD align=left><INPUT onclick=setAll(this.checked) type=checkbox value=69443 name=checkbox> </TD><TD class=displaytablerow align=left></TD><TD>AY363457 </TD><TD>A/swine/Hong Kong/312/00 </TD><TD>PB2 (1) </TD><TD>1183 </TD><TD>2000 </TD><TD>H3N2 </TD><TD></TD></TR><TR bgColor=white><TD align=left><INPUT onclick=setAll(this.checked) type=checkbox value=69442 name=checkbox> </TD><TD class=displaytablerow align=left></TD><TD>AY363456 </TD><TD>A/swine/Hong Kong/7220/00 </TD><TD>PB2 (1) </TD><TD>1212 </TD><TD>2000 </TD><TD>H3N2 </TD><TD></TD></TR><TR bgColor=#a7c4ef><TD align=left><INPUT onclick=setAll(this.checked) type=checkbox value=69441 name=checkbox> </TD><TD class=displaytablerow align=left></TD><TD>AY363455 </TD><TD>A/swine/Hong Kong/4361/99 </TD><TD>PB2 (1) </TD><TD>1211 </TD><TD>1999 </TD><TD>H3N2 </TD><TD></TD></TR><TR bgColor=white><TD align=left><INPUT onclick=setAll(this.checked) type=checkbox value=69450 name=checkbox> </TD><TD class=displaytablerow align=left></TD><TD>AY363464 </TD><TD>A/swine/Hong Kong/q066/99 </TD><TD>PB2 (1) </TD><TD>1231 </TD><TD>1999 </TD><TD>H3N2 </TD><TD></TD></TR><TR bgColor=#a7c4ef><TD align=left><INPUT onclick=setAll(this.checked) type=checkbox value=13158 name=checkbox> </TD><TD class=displaytablerow align=left></TD><TD>AF400761 </TD><TD>A/Swine/Hong Kong/2405/98 </TD><TD>PB2 (1) </TD><TD>1315 </TD><TD>1998 </TD><TD>H3N2 </TD><TD></TD></TR><TR bgColor=white><TD align=left><INPUT onclick=setAll(this.checked) type=checkbox value=13157 name=checkbox> </TD><TD class=displaytablerow align=left></TD><TD>AF400762 </TD><TD>A/Swine/Hong Kong/2422/98 </TD><TD>PB2 (1) </TD><TD>1315 </TD><TD>1998 </TD><TD>H3N2 </TD><TD></TD></TR><TR bgColor=#a7c4ef><TD align=left><INPUT onclick=setAll(this.checked) type=checkbox value=13156 name=checkbox> </TD><TD class=displaytablerow align=left></TD><TD>AF400763 </TD><TD>A/Swine/Hong Kong/2429/98 </TD><TD>PB2 (1) </TD><TD>1315 </TD><TD>1998 </TD><TD>H3N2 </TD><TD></TD></TR><TR bgColor=white><TD align=left><INPUT onclick=setAll(this.checked) type=checkbox value=6991 name=checkbox> </TD><TD class=displaytablerow align=left></TD><TD>AF251402 </TD><TD>A/Swine/Ontario/00130/97 </TD><TD>PB2 (1) </TD><TD>2311 </TD><TD>1997 </TD><TD>H3N2 </TD><TD></TD></TR><TR bgColor=#a7c4ef><TD align=left><INPUT onclick=setAll(this.checked) type=checkbox value=25207 name=checkbox> </TD><TD class=displaytablerow align=left></TD><TD>AF225516 </TD><TD>A/swine/Shizuoka/119/97 </TD><TD>PB2 (1) </TD><TD>2280 </TD><TD>1997 </TD><TD>H3N2 </TD><TD></TD></TR><TR bgColor=white><TD align=left><INPUT onclick=setAll(this.checked) type=checkbox value=25208 name=checkbox> </TD><TD class=displaytablerow align=left></TD><TD>AF225517 </TD><TD>A/swine/Shizuoka/120/97 </TD><TD>PB2 (1) </TD><TD>2280 </TD><TD>1997 </TD><TD>H3N2 </TD><TD></TD></TR><TR bgColor=#a7c4ef><TD align=left><INPUT onclick=setAll(this.checked) type=checkbox value=3854 name=checkbox> </TD><TD class=displaytablerow align=left></TD><TD>M73513 </TD><TD>A/Swine/Tennessee/24/77 </TD><TD>PB2 (1) </TD><TD>2341 </TD><TD>1977 </TD><TD>H1N1 </TD><TD></TD></TR><TR bgColor=white><TD align=left><INPUT onclick=setAll(this.checked) type=checkbox value=139333 name=checkbox> </TD><TD class=displaytablerow align=left></TD><TD>CY009923 </TD><TD>A/swine/Tennessee/25/77 </TD><TD>PB2 (1) </TD><TD>2309 </TD><TD>1977 </TD><TD>H1N1 </TD><TD></TD></TR><TR bgColor=#a7c4ef><TD align=left><INPUT onclick=setAll(this.checked) type=checkbox value=138706 name=checkbox> </TD><TD class=displaytablerow align=left></TD><TD>CY009635 </TD><TD>A/swine/31 </TD><TD>PB2 (1) </TD><TD>2313 </TD><TD>1931 </TD><TD>H1N1 </TD><TD></TD></TR><TR bgColor=white><TD align=left><INPUT onclick=setAll(this.checked) type=checkbox value=3616 name=checkbox> </TD><TD class=displaytablerow align=left></TD><TD>M55469 </TD><TD>A/Swine/Iowa/1976/31 </TD><TD>PB2 (1) </TD><TD>2326 </TD><TD>1931 </TD><TD>H1N1 </TD><TD></TD></TR><TR bgColor=#a7c4ef><TD align=left><INPUT onclick=setAll(this.checked) type=checkbox value=3858 name=checkbox> </TD><TD class=displaytablerow align=left></TD><TD>M73515 </TD><TD>A/Swine/Iowa/15/30 </TD><TD>PB2 (1) </TD><TD>2341 </TD><TD>1930 </TD><TD>H1N1 </TD></TR></TBODY></TABLE>

[Mamabird]

Re: New evidence of cytokine storm in avian flu cases

Is anyone curious as to why this research paper does not mention that the A/Vietnam/CL01/2004 sequence (DQ497719) used in the study has the E190D mutation in the HA segment? I would have thought that would have been a significant finding given that it makes the virus more human-like.