H5N1, is it spherical or filamentous ?

perhaps both : filamentous and spherical

about influenza virus in general :
  " Among clinical isolates that have
undergone a limited number of passages in eggs or tissue
culture, there are more filamentous than spherical particles,
whereas extensively passaged laboratory strains
consist almost exclusively of spherical virions (80-
120 nm in diameter). "

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by: maifair @ Sun Mar 25, 2007 at 12:58:32 PM CDT

cylindircal cross sections

End-on a cylinder looks like a circle, from the side, a rod.  So the circles in that photograph which are the same diameter as the rods are wide (narrowest dimension) and the rods are virus, the larger circles and fluffy stuff is MDKC cells innards.  Rods of varying lengths may simply be rods of the same length at different angles.

If you have trouble with color differentiation, try pulling the image up in a photo editing tool and fiddling (yeah, that's a technical term) with the 'hue' (changing the hue will change both colors relative to one another) or increasing saturation.

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by: a'Akova @ Mon Mar 26, 2007 at 00:08:11 AM CDT

700nm long

so, all the H5N1 viruses are filamentous, cylindrical ?
Or only some strains ? How is the Qinghai-strain ?
Any other flu-virus strains with this form ?

Assuming same volume as a spherical flu-A, I calculate
40nm diameter of the cross-section and 720nm of length.
This might have some advantage in penetrating the body,
penetrating masks.

However earlier pandemics were caused by spherical viruses,
maybe filamentous viruses can't so well transmit ?

When both forms of the same or similar virus can coexist,
then you have to wonder, which mutations in HA convert
is from spherical to filamentous ?

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by: gs @ Mon Mar 26, 2007 at 06:10:22 AM CDT

[ Parent ]

4 micrometer

I found, that flu is pleomorphic and can be 4 micrometer long !

pleomorphic adj. <"plE&'märfik/, /"plE&'mOrfik> Relating to or characterized by pleomorphism.

pleomorphism n. <"plE&'märfiz&m/, /"plE&'mOrfiz&m> The appearance of two or more distinctly different forms in the life cycle of some organisms. [ETYM: Greek pleo more + morphos form.]

---------------------------------------

well, viruses have no "life cycle" AFAIK.
So, does the shape depend on environment factors like
temperature or PH or pressure or chemical conditions ?

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by: gs @ Mon Mar 26, 2007 at 06:33:02 AM CDT

[ Parent ]

alignments

referring to picture
http://www.lib.uiowa...

everything which isn't gold seems to be green.
One cell can produce 100000-1000000 viruses, so is much larger.

When all viruses are filamentous with same cross-section
(diameter about 40nm)
then surprisingly many viruses are orthogonal to the screen-plane

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by: gs @ Mon Mar 26, 2007 at 07:02:33 AM CDT

[ Parent ]

a 2003-paper about that

thanks to Anne, who posted this link to FT:
http://vir.sgmjourna...
with some nice virus-pictures

J Gen Virol 84 (2003), 517-527; DOI 10.1099/vir.0.18803-0
Reverse genetics studies on the filamentous morphology of influenza A virus
Svetlana V. Bourmakina and Adolfo García-Sastre

A/WSN/33 (H1N1)  is spherical with diameter ~100nm
A/Udorn/72 (H3N2)  typically has 15% of virions larger than 400nm, while
they seem to be not much thinner than sherical virions, so the volume increases also.

The authors used reassorted and recombined versions to demonstrate
that the filamentous property is linked to the M1 gene and i.e.
to mutations R95K and E204D

"...The role that filamentous virus morphology may play in virus pathogenesis and disease is not known. Since long filamentous virions could theoretically infect neighbouring cells prior to their release, it has been suggested that filamentous virus morphology may facilitate cell-to-cell transmission of viruses in the respiratory mucosa (Roberts & Compans, 1998). On the other hand, small spherical virions would be expected to be more efficiently incorporated into aerosols and therefore may be easily transmitted from person to person. Future experiments are required to determine the biological role that filamentous viruses play in the influenza virus life-cycle and pathogenicity. The fact that clinical isolates of influenza A viruses invariably show filamentous phenotypes strongly suggests that this property is important for virus survival in nature. ..."

what is virus budding ?

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by: gs @ Sun Apr 01, 2007 at 04:25:30 AM CDT

questions...

is the filamentous property implied by mutations
or can the same virus be spherical at one time
and filamentous at another time and how is this triggered ?

Do masks filter filamentous particles better ?
Is either sort needed to enter a human and infect cells ?

If WSN comes without filamentous virions, then why is it needed
at all ? What is it good for ?
What percent of filamentous virions do the 1918,1957,1968
pandemic strains have, how many has H5N1 ?

One other remarkable quote from that paper:

"The formation of extremely long cord-like structures with lengths
up to 500micrometer has been described upon infection of cells
with some influenza-C virus strains (Nishimura et al.,1990)"

that's half a millimeter long , so it could be seen
if it weren't so thin.

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by: gs @ Sun Apr 01, 2007 at 04:45:39 AM CDT

[ Parent ]

virus budding

is how flu viruses are released from the cell.

Flint p477:

"The release of enveloped virus particles from the plasma membrane is a complex process that comprises induction of membrane curvature by viral components (bud formation), bud growth and fusion of the bud membrane. Although budding has been visualised repeatedly, often in striking images, the mechanisms of this crucial process are still not well understood."

(there follows most of a page on the mechanism, but I'm not typing the whole thing!)

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by: Mathematician @ Sun May 13, 2007 at 06:17:01 AM CDT

[ Parent ]

budding

so, what's "budding" ?
And what has it to do with several viruses possibly joining
together to form filamentous (poly-)viruses ?
This could happen anywhere, in or outside cells.

Well, probably not, else it would have been mentioned somewhere.
But I can't see why.

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by: gs @ Sun May 13, 2007 at 06:28:45 AM CDT

[ Parent ]

subject

sorry, I had missed your subject line and thus the context.
There were these fluorescent pictures in the Garcia-Sastre paper
quoted above, assumed to happen through budding.

From the neuraminidase inhibitors discussion I was
assuming, the cell would just burst.

What would happen, if viruses couldn't exit the cell ?
The cell eventually dies earlier or later anyway
but time could be important in the race against the immune-system.

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by: gs @ Sun May 13, 2007 at 13:18:15 PM CDT

[ Parent ]

If I understand correctly

some viruses work by making the cell burst to let the new virions out, and others by budding. (Maybe it's as simple as that enveloped viruses, like influenza, work by budding and unenveloped ones by making the cell burst? Don't have the book to hand...) Anyway, influenza works by budding. I *think* I understand that the cell normally dies anyway, within 24-48 hours of infection, but virions are released gradually in multiple instances of budding. I think I've read that it's not quite clear why the cell eventually dies.

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by: Mathematician @ Sun May 13, 2007 at 13:56:42 PM CDT

[ Parent ]

OK, there is also something in the wiki:

http://www.fluwikie....

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by: gs @ Sun May 13, 2007 at 14:26:05 PM CDT

[ Parent ]

and here:

http://www.ncbi.nlm....

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by: gs @ Sun May 13, 2007 at 15:40:02 PM CDT

[ Parent ]

chains

see pictures I,J,K  here:

http://jvi.asm.org/c...

http://jvi.asm.org/c...

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by: gs @ Mon May 14, 2007 at 00:13:14 AM CDT

[ Parent ]

hmm, very interesting!n/t

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by: Mathematician @ Mon May 14, 2007 at 03:55:38 AM CDT

[ Parent ]

lots of free papers

actually, there are lots of free papers at JVI,
even lots about budding, filamentous influenza.

You can just follow the links in the references or
to the articles where the actual one is quoted.

lots of virus pictures too !

I didn't find, that spherical viruses would join to
form filamentous ones, so they probably don't.
The viruses are formed by the budding and then
probably remain how they were created.
These long viruses could be almost empty - I'm not sure.

Also unclear to me how they differ in infectivity.
H5N1 is filamentous ... maybe that's why we have no
efficient h2h, who knows.

Influenza C can form very long filamentous viruses,
0.5mm long !

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by: gs @ Mon May 14, 2007 at 05:26:45 AM CDT

[ Parent ]

picture

http://magictour.fre...

more pictures at
http://health.ph.gro...

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by: gs @ Fri Oct 12, 2007 at 02:47:37 AM CDT

[ Parent ]

yours "not found on this server" :-( n/t

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by: Mathematician @ Fri Oct 12, 2007 at 03:41:16 AM CDT

[ Parent ]

url

http://magictour.fre...

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by: gs @ Fri Oct 12, 2007 at 04:04:06 AM CDT

[ Parent ]

100nm

it says bar equals 1 nm, but I think it must be
bar=100nanometer=0.1micrometer

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by: gs @ Fri Oct 12, 2007 at 04:06:05 AM CDT

[ Parent ]

interpretation

in the lower picture you can see some larger "pieces",
I assume they have nothing to do with H5N1, what are they ?

Also one long bended thinner filament in the top middle of the
lower picture, about 600nm long and 30nm thick.
Is it also H5N1 ?
In its middle you see a small spherical virus(?) of about
60nm in diameter only.
Also some smaller spherical pieces with about 30nm diameter
only, but without the characteristical dark field in the middle,
so I'm not sure it's H5N1.
When 2 of the long filaments cross, you can see "through" the viruses.
Some irregular shaped "things" in the upper picture.

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by: gs @ Fri Oct 12, 2007 at 04:25:02 AM CDT

[ Parent ]

morphology

from the Shortridge et.al. paper:

The H5N1 viruses isolated from chickens and humans showed slight differences
in morphology (Fig.4).On electron microscopy, the chicken virus showed a
mixture of long filamentous(35%;N=161) and sherical virions.
The virus isolated from humans was predominantly spherical, with a few
filaments (16%;N=220).

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by: gs @ Fri Oct 12, 2007 at 04:29:24 AM CDT

[ Parent ]

Scale and interpretation

I just *wonder* whether *maybe* the scale given is correct, and what we're looking at there is the surface of one or more virions. Then the rod shaped things would be the H5, the mushroom/spherical bits the N1. That would be amazing... But it's always best to assume that there isn't a mistake, if possible (so we should take the scale as read if at all possible), and I did find text somewhere saying that under TEM H seems rod-like and N mushroom-like (i.e., that it is possible to see that much detail), and if most of the picture is something else, it's odd that the caption doesn't say what it is. (Compare the CDC micrograph that's everywhere, where it tells you that the gold is H5N1 and the green the MDCK cells in which it's grown.)

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by: Mathematician @ Fri Oct 12, 2007 at 04:47:41 AM CDT

[ Parent ]

joining viruses ?

just a spontaneous, maybe silly idea:

the filamentous viruses, could it just be several spherical
ones joining together ?

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by: gs @ Sun May 13, 2007 at 04:16:16 AM CDT

don't think so

the structures are pretty well understood (even if the functions aren't). Recently acquired a copy of Flint's Virology - recommended :-)

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by: Mathematician @ Sun May 13, 2007 at 06:07:34 AM CDT

[ Parent ]

how to bud

I just saw this picture :

http://img.stern.de/img/1p.gif

and it seems, that the filamentous viruses "bud" through the cell
in longitudinal direction. That may give them a thinner membrane ?

For some reason I'd thought all the time they would bud with their
big surface.

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by: gs @ Wed Jan 02, 2008 at 11:20:48 AM CST

link

sorry, the correct link is:
http://www.stern.de/grippe/erk...

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by: gs @ Wed Jan 02, 2008 at 11:23:21 AM CST

[ Parent ]

2006-paper

here is a paper from 2006, which I found good readable:
http://www.pnas.org/cgi/reprin...

quote:
-----------------------------------
we have considered some possible relationships between spherical
virions and elongated ones; for instance that spherical virions
may bud in the same way but simply have piched off earlier.
However, this hypothesis does not square with the observation that
most spherical virions have larger diameters (120 vs.100 nm)
,Alternatively, could spherical virions be derived from elongated ones
by an in vitro rearrangement in overall structure accompanied by a
disordering of the RNPs ? [the 8 ribonucleotide proteins]
This hypothesis, although not ruled out, invokes a major reorganization
of the matrix layers after budding.
--------------------------------------------

this assumes elongated viruses were normal,
but on budding pictures we usually see spherical viruses.
My thought would be, that spherical virions (=viruses)
are normal and they might join later to form
filamentous (=elongated) viruses, but this is
not supported by others.
With the X-31 viruses from the paper they had only slightly
elongated viruses, but H5N1 on pictures is often
5 fold elongated. (long axis vs. short axes)
Where are the RNPs in those loong viruses ?
Do they have multiple sets ?
When they are arranged parallel to the long axis,
how to they attach to the matrix layer ?

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by: gs @ Sun Jun 08, 2008 at 08:24:55 AM CDT

[ Parent ]

Mexflu

filamentous in this picture ?
http://images.ctv.ca/archives/...

or two sperical ones near each other

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by: gs @ Sat May 16, 2009 at 03:03:46 AM CDT

[ Parent ]

Udorn/1972(H3N2)

http://www.ncbi.nlm.nih.gov/pu...
Abstract
Influenza is a lipid-enveloped, pleomorphic virus. We combine electron cryotomography and analysis of images of frozen-hydrated virions to determine the structural organization of filamentous influenza A virus. Influenza A/Udorn/72 virions are capsule-shaped or filamentous particles of highly uniform diameter. We show that the matrix layer adjacent to the membrane is an ordered helix of the M1 protein and its close interaction with the surrounding envelope determines virion morphology. The ribonucleoprotein particles (RNPs) that package the genome segments form a tapered assembly at one end of the virus interior. The neuraminidase, which is present in smaller numbers than the hemagglutinin, clusters in patches and are typically present at the end of the virion opposite to RNP attachment. Incubation of virus at low pH causes a loss of filamentous morphology, during which we observe a structural transition of the matrix layer from its helical, membrane-associated form to a multilayered coil structure inside the virus particle. The polar organization of the virus provides a model for assembly of the virion during budding at the host membrane. Images and tomograms of A/Aichi/68 X-31 virions show the generality of these conclusions to non-filamentous virions.

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by: gs @ Thu May 27, 2010 at 07:48:32 AM CDT

[ Parent ]