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list of reassortment studies

gsgs

gsgs

Registered User
who helps with that pubmed reassortment meta-study ?
making a list of the viruses,species,(lab),reassorted segments,dates, from the studies

motivation is, of course, to get a feeling for what we can expect with H7N9,
when we can see first experiments and results

I managed to create and attach a file with the 725 abstracts to this post !




pubmed reassortment influenza 725 hits
http://www.ncbi.nlm.nih.gov/pubmed/?term=reassortment+influenza

pubmed reassortment influenza ferret(s) 37(36) hits
http://www.ncbi.nlm.nih.gov/pubmed/?term=reassortment+influenza+ferrets

pubmed reassortment influenza mouse(mice) 83(81) hits
http://www.ncbi.nlm.nih.gov/pubmed/?term=reassortment+influenza+mouse

pubmed reassortment influenza guinea 7 hits
http://www.ncbi.nlm.nih.gov/pubmed/?term=reassortment+influenza+guinea

pubmed reassortment influenza pig(s)[swine] 225(238)[216] hits
http://www.ncbi.nlm.nih.gov/pubmed/?term=reassortment+influenza+pig

pubmed reassortment influenza horse(s) 14(14) hits
http://www.ncbi.nlm.nih.gov/pubmed/?term=reassortment+influenza+horses

pubmed reassortment influenza cell culture(s) 16(10) hits
http://www.ncbi.nlm.nih.gov/pubmed/?term=reassortment+influenza+cell+culture

pubmed reassortment influenza chicken(s) 119(86) hits
http://www.ncbi.nlm.nih.gov/pubmed/?term=reassortment+influenza+chicken

pubmed reassortment influenza mallard(s) 12(9) hits
http://www.ncbi.nlm.nih.gov/pubmed/?term=reassortment+influenza+mallard

pubmed reassortment influenza duck(s) 106(78) hits
http://www.ncbi.nlm.nih.gov/pubmed/?term=reassortment+influenza+ducks



--------------------------------------------------------------------
reassortment studies with ******:

Mar.2011 http://www.ncbi.nlm.nih.gov/pubmed/21195732 cell culture,WI
Feb.2011 http://www.ncbi.nlm.nih.gov/pubmed/21291589 ferrets,NL, H1N2
July 2011 http://www.ncbi.nlm.nih.gov/pubmed/21730147 ferrets,MD, H9N2
Mar 2013 http://www.ncbi.nlm.nih.gov/pubmed/23302886 ferrets,MD,H1N2
July 2011 http://www.ncbi.nlm.nih.gov/pubmed/21507962 mice,Korea,H3N2,H5N1
July 2011 http://www.ncbi.nlm.nih.gov/pubmed/21799774 mice,Beijin,guinea pigs,triple
Sept.2011 http://www.ncbi.nlm.nih.gov/pubmed/21849283 mice,TW,H1N1(PA!)
May 2012 http://www.ncbi.nlm.nih.gov/pubmed/22323532 mice,UK,H3N2,PR34
Feb.2013 http://www.ncbi.nlm.nih.gov/pubmed/23221570 mice,JP,Mex

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


threads in this subforum (not so easy to make it clickable)

Code: 
VJ: Experimental infection with a Thai reassortant swine influenza virus of pandemic     H1N1 origin induced disease     tetano March 16th, 2013
Characterization of influenza virus reassortants based on new donor strain   A/HK/1/68/162/35(H3N2)    tetano March 16th, 2013
A comprehensive analysis of reassortment in influenza A virus    tetano March 10th, 2013
Reassortment Complements Spontaneous Mutation in Influenza A Virus NP and    M1 genes to Accelerate Adaptation to a New Host    tetano February 2nd, 2013
In vivo selection of H1N2 influenza virus reassortants in the ferret model    tetano January 12th, 2013
New approaches for unravelling reassortment pathways      tetano January 5th, 2013
Possible outcomes of reassortment in vivo between wild type and live attenuated   influenza vaccine strains   tetano October 17th, 2012
Pathogenicity and transmissibility of reassortant H9 influenza viruses with genes   from pandemic H1N1 virus   tetano August 11th, 2012
Viral reassortment as an information exchange between viral segments    tetano Feb 18th, 2012
An influenza reassortant with polymerase of pH1N1 and NS gene of H3N2 influenza A virus   is attenuated in vivo     February 11th, 2012  by tetano
Polymerase activity of hybrid ribonucleoprotein complexes generated from reassortment    between 2009 pandemic H1N1 and seasonal H3N2 influenza A viruses   tetano Dec 12th, 2011
A Novel Reassortant Canine H3N1 Influenza Virus between Pandemic H1N1 and   Canine H3N2 Influenza Viruses in Korea   tetano December 5th, 2011
Palindromes drive the re-assortment in Influenza A    tetano December 4th, 2011
Reassortment and mutation of the avian influenza polymerase PA subunit overcomes   species barriers  tetano November 18th, 2011
Novel genetic reassortants in H9N2 influenza A viruses and their diverse pathogenicity   to mice    tetano November 4th, 2011
Reassortant H9N2 Influenza Viruses Containing H5N1-Like PB1 Genes Isolated from    Black-Billed Magpies in Southern China    tetano October 10th, 2011
H9N2 avian influenza viruses and pH1N1 virus can reassort and generate novel    viruses with respiratory transmission potential in mammals  Gert van der Hoek Sep 18th, 2011
Increased pathogenicity of a reassortant 2009 pandemic H1N1 influenza virus containing   an H5N1 hemagglutinin   tetano September 16th, 2011
Altered Pathogenicity for Seasonal Influenza Virus by Single Reassortment of the RNP   Genes Derived From the 2009 Pandemic Influenza Virus   tetano August 20th, 2011
When Flu Strains 'Hook Up,' Dangerous Progeny Can Result    tetano July 14th, 2011
Reassortment between seasonal H1N1 and pandemic (H1N1) 2009 influenza viruses   is restricted by limited compatibility among polymerase subunits   tetano June 22nd, 2011
ProMed: H3N2/H1N1 REASSORTANT ex PATIENT    Tonka June 9th, 2011 06:52 PM
reassortment database    gsgs May 29th, 2011
Reassortant Pandemic (H1N1) 2009 Virus in Pigs, United Kingdom    tetano May 25th, 2011 08:35 PM
Virulence and genetic compatibility of polymerase reassortant viruses derived from the pandemic (H1N1) 2009 virus and circulating influenza A viruses   tetano April 23rd, 2011
N-Glycans from Porcine Trachea and Lung: Predominant NeuAcα2-6Gal Could Be a Selective Pressure for Influenza Variants in Favor of Human-Type Receptor   tetano February 26th, 2011
germany/ reassortant H1N1 in pigs   Anne February 12th, 2011
Possible Increased Pathogenicity of Pandemic (H1N1) 2009 Influenza Virus upon Reassortment   tetano February 5th, 2011
The nonadaptive nature of the H1N1 2009 Swine Flu pandemic contrasts with the adaptive facilitation of transmission to a new host   tetano January 8th, 2011
Reassortment between seasonal and swine-origin H1N1 influenza viruses generates viruses with enhanced growth capability in cell culture   tetano January 5th, 2011
Reassortment of Ancient Neuraminidase and Recent Hemagglutinin in Pandemic (H1N1) 2009 Virus,   tetano September 30th, 2010
Genetic characterization of 2008 reassortant influenza A virus (H5N1), Thailand   tetano September 16th, 2010
Scientists prove humans can have two flus at once   tetano September 16th, 2010
Reassortant between Human-Like H3N2 and Avian H5 Subtype Influenza A Viruses in Pigs: A Potential Public Health Risk   tetano September 15th, 2010
Reassortment of pandemic H1N1/2009 influenza A virus in swine   tetano August 10th, 2010
Kawaoka: hybridization of H1N1 and H5N1   tetano August 5th, 2010
Evidence Obtained from anova to Reason Cross-species Infection and Cross-subtype Mutation in Neuraminidases of Influenza A Viruses   tetano June 17th, 2010
A phylogenetic approach to detecting reassortments in viruses with segmented genomes   tetano June 17th, 2010
Viral reassortment and transmission after coinfection of pigs with classical H1N1 and triple reassortant H3N2 swine influenza viruses   tetano May 21st, 2010
Chinese study: a case of H1N1-H3N2 (seasonal) hybrid virus   tetano May 13th, 2010
graphics of evolution of PB1 since 1968   gsgs December 16th, 2009
will newflu reassort with oldflu ?   gsgs August 26th, 2009
Reassortment Patterns in Swine Influenza Viruses  sharon sanders August 22nd, 2009
seasonal H1N1, 2006/7  gsgs August 22nd, 2009
Reassortment of the Influenza Virus Genome    Chuck July 7th, 2009
Reassortment between avian H5N1 and human H3N2 influenza viruses in ferrets   Anne June 6th, 2009
what reassortments can we expect in pandemic flu now ?   gsgs June 1st, 2009
reassortments in swine  gsgs June 1st, 2009
5% have 2 viruses   gsgs May 30th, 2009
H1N1 Related to Virus Born on Hog Factories in 1998   Veg May 3rd, 2009
|A STUDY: Deviation from the random distribution pattern of influenza A virus...|_   Giuseppe Michieli April 19th, 2008
Reassortant Avian Influenza Virus (H5N1) in Poultry, Nigeria, 2007  sharon sanders March 26th, 2008
Bird flu genes found in new swine flu  Coleman December 22nd, 2007
similarity of the 16 HAs   gsgs August 29th, 2007
H3N2, 1976   gsgs April 2nd, 2007
The use of the word, "reassortment".  GaudiaRay November 9th, 2006
New data show how bird flu quickly spreads  Harriet August 19th, 2006
Tests suggest bird flu hybrids not big threat  Snowy Owl August 1st, 2006


...
 

Attachments

Last edited:
Re: list of reassortment studies

counts of seroptypes mentioned in that file of 725 abstracts:

Code: 
    183,H
      3,H0N1

     62,H1
      1,H1pdm 
    825,H1N1
     35,H1N1pdm
      1,H1N1pps
      2,H1N1s 
     15,H1N1v 
    126,H1N2
      1,H1N3
      2,H1N8
      1,H1N9 

     18,H2 
      1,H2H2
      2,H2N1 
     53,H2N2
      9,H2N3
      2,H2N5 

     48,H3
     12,H3N1
    483,H3N2
      1,H3N2s
      5,H3N2v
      5,H3N6
     30,H3N8

      9,H4
      1,H41P 
      1,H4N
      1,H4N1 
     10,H4N2
     14,H4N6
      4,H4N8
      3,H4N9

    102,H5
    656,H5N1
     61,H5N2
     16,H5N3
      3,H5N5
      1,H5N8
      8,H5N9

     44,H6
     24,H6N1
     34,H6N2
      3,H6N5
      5,H6N6
     12,H6N8
      1,H6N9 

     63,H7 
     10,H7N1
      5,H7N2
     18,H7N3
     39,H7N7 

      2,H8N4

     42,H9
      4,H9N1 
    290,H9N2 
      1,H9N6 
      8,H9N8
      2,H10 
      3,H10N3 
     12,H10N7
      2,H10N8 

      3,H11
      3,H11N1
      2,H11N2
      4,H11N3
      1,H11N6
      5,H11N9

      1,H12N3 

     12,H13 
      9,H13N2
      2,H13N6 
      1,H13N8
      1,H13N9 

     10,H14 

      4,H15
      2,H15N4

      3,H16
      4,H16N3
      1,H16N6 

      1,H17
 
Re: list of reassortment studies

hey, I didn't know that you can easily download all the abstracts from pubmed !
72002 influenza abstracts in 88MB

779524 hits for "virus" , that could be~ 1GB
21286702 hits for "journal"

eassort : 1537
eassort,H7 : 96
eassort,H9 : 136
eassort,N9 : 17
eassort,N2 : 662 (presumably because of H3N2)

I attach the 3 smaller files
 

Attachments

Re: list of reassortment studies

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3604002/
Reassortment between Avian H5N1 and Human Influenza Viruses
Is Mainly Restricted to the Matrix and Neuraminidase Gene Segments
H1N1, H3N2 and pandemic H1N1
human NA and MP were preferentially selected by H5
these H5 reassortants did not show a marked increase in replication
in MDCK cells and human bronchial epithelial cells.
In ferrets, inoculation with a mixture of H5N1-pandemic H1N1 reassortant
viruses resulted in outgrowth of (aaaaahha) viruses
This virus was not transmitted via aerosols or respiratory droplets
to naïve recipient ferrets.
-------------------------------------------------------
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3141953/
Compatibility of H9N2 avian influenza surface genes and 2009 pandemic H1N1 internal
genes for transmission in the ferret model
(33393933) could gain efficient respiratory droplet transmission ferrets
1P10:111p11111 (best)
2P10:111p1p111 ok
1wf10:111w1111 no
2wf10:111w1w111 a bit
1:A/NL/602/09(H1N1),p:A/ferret/MD/P10-UMD/08(H9N2),w:A/guinea fowl/HK/WF10/00(H9N2)
---------------------------------------------------------------
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3054021/


http://www.ncbi.nlm.nih.gov/pubmed/22875253
99999999 (G1) bad in pigs
11111111 good in pigs
11191111 good in pigs
11191911 good in pigs
 
Re: list of reassortment studies

http://jvi.asm.org/content/early/2011/09/14/JVI.05582-11.short
(1:H1N1pdn,2009 , 5:H5N1,1997)
increased replication of 11151111 in epithelial cells ,(others 7+1 reduced) , 100% lethal to mice
Serial passage of 11111111 or 11151111 in cells increased pathogenicity
Serial passage of 55555555 attenuated

Coinfection of MDCK cells with 1 and 5 gave singlegene reassortants in vitro
single-gene reassortment is common among H1N1 and H3N2 i.e. with HA

tested in MDCK cells ,human A549 cells ,normal human bronchial epithelial cells (NHBE)

11111111 was mild in mice with <10% weightloss , also 51111111,15111111,11511111,11115111,11111115
11151111 and 55555555 100% lethal
11111511 and 11111151 : no weithloss

serially passaged 3 times in differentiated NHBE cells cultured at the air-liquid interface
11111111 and 11151111 replicated to high titers , 55555555 attenuated after passage 2
11151111 100 fold of 11111111

11111111(p3,3 passages) 11151111(p3) more weight loss than p0.
11111111 transmits in ferrets 11151111 and 55555555 not
Octaviani et al. found that 15555555,51555555,11555555 had enhanced growth in A549-M2 cells
transmissibility is a multigenic trait, involving the PB2

-------------------------------------------------------
Kawaoka et.al.
Experimental adaptation of an influenza H5 HA
confers respiratory droplet transmission to a
reassortant H5 HA/H1N1 virus in ferrets

11151111 + --> droplet in ferrets

avian H3 Q226L
avian H5 Q226L not
Q226L and G228S, increased
Q226L and N224K yes (2,6)

E119G/V152I/N224K/Q226L
-------------------------------------------------
http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1000709
Dec.2009,guinea pigs,701(PB2),158-160(HA)
---------------------------------------------------------
 
Re: list of reassortment studies

Kimble et.al:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3141953/
Compatibility of H9N2 avian influenza surface genes and 2009 pandemic H1N1
internal genes for transmission in the ferret model

reassortant virus composed of wild-type avian H9N2 surface genes in a
seasonal human H3N2 backbone could gain efficient respiratory droplet
transmission in the ferret model.

Experimentally, H9N2 surface genes reassorted with
seasonalH3N2internalgeneshaveshownefficienttransmissionin
a ferret model only after adaptation by serial passage and in-
corporation of amino acid changes on the surface and internal
genes (15)

All four viruses were made with the pH1N1 internal
genes (PB2, PB1, PA, NP, M, and NS) from A/Netherlands/602/
2009 (H1N1) (20). The surface genes came from either A/guinea
fowl/Hong Kong/WF10/1999 (H9N2) or from A/ferret/Mary-
land/P10_UMD/2008 (H9N2), herein referred to as WF10 and
P10, respectively (15, 21).

The P10 virus is the result of 10 serial passages in
ferrets of an avian-human H9N2:H3N2 reassortant containing
the WF10 surface on a seasonal H3N2 (A/Memphis/14/1998)
backbone (15).

(T189A in HA1 and G192R in HA2) and one in the NA (I28V)
compared with the WF10

These amino acid changes were shown
to be crucial for efficient and reproducible respiratory droplet
transmission in ferrets (15). The four viruses generated in this
report had P10 HA and NA (2P10), P10 HA and pH1N1 NA
(1P10), WF10 HA and NA, (2WF10) or WF10 HA and pH1N1
NA (1WF10) (Fig. 1A).

2P10:
1P10:
2WF10:
1WF10:


Sorrell EM, Wan H, Araya Y, Song H, Perez DR (2009) Minimal molecular constraints
for respiratory droplet transmission of an avian-human H9N2 influenza A virus. Proc
Natl Acad Sci USA 106:7565–7570

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

. Sun Y, et al. (2011) High genetic compatiblity and increased pathologenicity of
reassortants derived from avian H9N2 and pandemic H1N1/2009 influenza viruses.
Proc Natl Acad Sci USA 108:4164–4169.
http://www.pnas.org/content/early/2011/02/23/1019109108

people in China, ranging from 13.7% to 37.2%, might have ev-
idence of prior infections of the H9N2 virus (11, 12).

A/chicken/Hebei/LC/2008, HB08) and a pan-
demic H1N1 influenza virus (A/Beijing/16/2009, BJ09)



the virus is very poultry-adapted
in the inner segments. As was the 1997
Hong Kong virus, a reassortant from chickens.
It was not in wild birds and they could wipe
it out. The ~2002 recurrent H5N1 was not so
much a poultry virus (#amino acid mutations in segment 8 etc.), it was in wild birds and did
spread and still persists. I think chances are good that they can wipe out this H7N9.
Testing must be increased since it's LP, but they can do that.
 
Re: list of reassortment studies

not really about reassortment, but related, since it deals with H7-viruses,
even H7N9 ones, although from the American lineage.

> Several high and low pathogenicity H7N3 and H7N9 viruses replicated
> efficiently in the respiratory tract of mice without prior adaptation following
> intranasal inoculation, but only MX/7218 virus caused lethal disease in this
> species. H7N3 and H7N9 viruses were also detected in the mouse eye
> following ocular inoculation. Virus from both H7N3 and H7N9 subtypes
> replicated efficiently in the upper and lower respiratory tract of ferrets,
> however, only MX/7218 virus infection caused clinical signs and symptoms
> and was capable of transmission to naïve ferrets in a direct contact model.
> Similar to other highly pathogenic H7 viruses, MX/7218 replicated to high
> titers in human bronchial epithelial cells, yet downregulated numerous
> genes related to NF-κB-mediated signaling transduction.

--------------------------------------------------------------------------------------------
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3577880/
we have quantitatively characterized the glycan receptor-binding specificity of HAs from representative
strains of Eurasian (H7N7) and North American (H7N2) lineages that have caused human infection.
Furthermore, we have demonstrated for the first time that two specific mutations; Gln226→Leu and
Gly228→Ser in glycan receptor-binding site of H7 HA substantially increase its binding affinity to human
receptor

Introducing the double Gln226→Leu/Gly228→Ser mutations on FC (mFC:LS) and CC (mCC:LS) resulted in
binding to both avian and human receptors
The FC, CC and NY/107 strains were also previously analyzed for their ability to transmit in the ferret
animal model NY/107 and the highly pathogenic CC strain showed some transmission via direct
contact, however the other highly pathogenic strain isolated from fatal case did not show any transmission.
None of the viruses transmitted via respiratory droplets.
We previously demonstrated that the human receptor-binding specificity and affinity correlates with
respiratory droplet transmissibility in ferrets.
We demonstrated that the double Gln226→Leu/Gly228→Ser mutation (hallmark changes for
human adaptation of H3 and H2 HA) dramatically increased human receptor-binding affinity
of FC and CC HA
(A/Netherlands/230/03 referred to henceforth as CC
A/Netherlands/219/03 henceforth referred to as FC

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

copy of post 4 from the other thread:
2 other papers about h9n2 evolution

http://www.ncbi.nlm.nih.gov/pubmed/22416344
Samples of chicken, duck, quail, and pigeon were collected from Jiangsu, Anhui,
and Hebei in 2009-2011
amino acid motif of cleavage sites in the HA gene was P-S-R/K-S-S-R
Leucine (L) at the amino acid position 226 in the HA
AIVs originated from F98-like virus as backbone and formed two new genotypes through
reassortment with HA gene of Y280-like virus and PB2 and M genes of G1-like virus

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

http://www.plosone.org/article/info:...l.pone.0049224

there is variable homology among the various NA subtype sequences, especially
in the N1 and N2 subtypes with the deletion of 4~30 amino acids in the stalk domain [23,1993]
Meanwhile, the factors that influence NA include deletion of the stalk domain,
the mutations drug-resistance, as well as the changing of antigen sites or glycosites
and the variation of the topology of N-glycan structures [28,2011].
The pattern of stalk domain deletion in N2 NA is distinctive in different combinations of IVs.
The representative NA sequences in each available N2 subtypes are aligned in the stalk domain.
As can be observed, the number of deletions varies from 4 to 24 residues,
causing the loss of one or two potential glycosites.
9 NA subtypes are concentrated into two evolutionary groups: one group was represented by
N2 and contains N3, N6, N7, and N9; and another group contains N1, N4, N5, and N8.

deletion of 3 residues and one corresponding glycosite with the pattern “E-R-61N-3-64T-V-H”
(meaning 3 residues missing between 61N and 64T, e.g., A/chicken/Zhejiang/611/2011 (H9N2)),
appeared in most of the NA subtypes of the H9N2 virus.

---------------------------------------------------------------
 
Last edited:
Re: list of reassortment studies

http://www.plosone.org/article/info:doi/10.1371/journal.pone.0059550
Although the Kd' ~300 pM for WF10 HA binding to human receptor is 5 fold higher
than that of 2009 H1N1 HA [7], a reassorted virus with HA and NA from WF10 and
other internal genes from a human-adapted H3N2 virus did not show respiratory droplet
transmission in ferrets [15].

Repeated passaging of this reassorted virus in ferrets led to a strain (RCP10) that had
additional mutations in HA and NA and transmitted via respiratory droplets in ferrets.
One of the mutations Thr-189→Ala is in the RBS of H9 HA while the other mutation
is in HA2 close to the transmembrane region (unlikely to impact RBS features and
hence receptor binding). It was demonstrated that both these mutations are needed
for conferring respiratory droplet transmission.
Thr-189→Ala mutation is needed
H9 HA a single mutation Q226L might be sufficient
Leu-226 in context of His-156 and Lys-137 in the Qa88 RBS provides a more optimal
environment than Leu-226 in the context of Gln-156 and Arg-137 in WF10 RBS for
achieving a higher quantitative human receptor affinity
While H9N2 subtype is yet to adapt to the human host, reassorted strains with H9 HA
and NA have acquired as few as 2 amino acid changes in HA and a single Ile-28→Val
change in NA to confer respiratory droplet transmission in ferrets
Such an outcome has not been possible with HAs from other avian subtypes
 
Re: list of reassortment studies

http://www.sciencemag.org/content/early/2013/05/01/science.1229455

both PA and NS of H1N1 made H5N1
transmissible by droplet in guinea pigs, without death


http://www.nature.com/news/scientists-create-hybrid-flu-that-can-go-airborne-1.12925

could spread through the air between guinea pigs in adjacent cages, as long as they carried
either or both of two genes from H1N1 called PA and NS


but in 293T cells 6,7,8 were selected from H1N1p , 67 from H3N2, 6,7 from H1N1s
in MDCK cells few differences , NA alone was worse
in wdNHBE cells wt was best
in ferrets 6,7(1) were selected from the mix
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3604002/
Reassortment between Avian H5N1 and Human Influenza Viruses
Is Mainly Restricted to the Matrix and Neuraminidase Gene Segments
H1N1, H3N2 and pandemic H1N1 , post 4 above
 
Re: reassortment studies

Re: reassortment studies

http://www.ncbi.nlm.nih.gov/pubmed/23639426
> Conversely, HA and each of the three polymerase segments, alone or in combination,
> of the avian influenza viruses mainly reassorted in the A/H1N1pdm09 virus backbone.

I'm not sure, what that means. 55551111 reassorts or 71771111 or 11191111 ?

> Of note, A/H1N1pdm09 viruses that reassorted with HA of H1N1 seasonal human or
> H11N6 avian viruses or carried different combination of avian origin polymerase segments,
> exerted a higher replication effectiveness than that of the parental viruses.

111s1111 , 111e1111 , 55511111 , 71711111 all replicate better than 11111111

> These results confirm that reassortment of the A/H1N1pdm09 with circulating low pathogenic
> avian influenza viruses should not be misjudged in the prediction of the next pandemic.

nothing should be misjudged in any prediction

----------------------------------------------------------------------------
http://www.ncbi.nlm.nih.gov/pubmed/23639426
well working reassortments in A549 cells are:

111s1111 (?)
x11x1111
1x1x1111
11xx1111
xxxx1111

111s1111
111e1111
a1111111,1a111111,11a11111,aa111111,1aa11111,a1a11111,aaa11111

1:H1N1pdm,a:avian,e:H11N6,s:old seasonal H1N1,x:{H1N1,H3N2,H11,H10,H9,H7,H1av}

-------------------------------------------------------------------------------
 
Re: list of reassortment studies

Josh P. • 4 hours ago
−+

..I agree with your Vincent, this is quality science and much more relevant than the gain of function
experiments done last year in ferrets. I will tell you this, the PA segment of H1N1 is a nasty ******.
I find this segment increases the replication fitness within seven segments of H3N2 swine over the
parent strain in both human and swine cells when I make reassortments. The more alarming scenario
that isn't mentioned is that multiple genome segments of pH1N1 are circulating in the swine population
right now..including pH1N1 PA. However there is a little surveillance data on internal influenza genes
as mostly just sequencing is done with NA, HA and sometimes M. I hypothesize based on my co-infection
reassortment studies in swine (Hopefully some upcoming animal data) and data in the influenza online
database (although limited) that the PA gene segment of pH1N1 will be an issue for years to come.
I bet if you took H7N9 and replaced the PA gene with pH1N1 you would get a very nasty virus...this
could very well happen in pigs. 50 million pigs in the H7N9-infected region, knowing how reassortments
behave is VERY important.
 
Re: list of reassortment studies

2011: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3143117/

e=A/swine/Fujian/204/2007 (H1N1)
t=A/swine/Guangdong/1222/2006 (H1N2)
rH1N1=ttttteet

rH1N1 in mice had higher replicability and pathogenicity than sH1N1,eH1N1
but similar to the pH1N1 and tH1N2
in guinea pigs rH1N1 was not transmissible, but p2009 was
HA and NS contributed to the transmission of pH1N1.
HA+NA of pH1N1 gave good contact transmission among guinea pigs.
-----------------------------------------------------------------------
[A/Swine/Korea/1204/2009; Sw/1204 (H1N2)] was virulent in ferrets, causing death within
10 d of inoculation, and was efficiently transmitted to naive contact ferrets via respiratory droplets
the TRS viruses were moderately pathogenic in ferrets and grew efficiently in both the upper and
lower respiratory tracts. All North American TRS viruses studied were transmitted between ferrets
via direct contact. However, their transmissibility by respiratory droplets was related to their HA
and NA lineages: TRS viruses with human-like HA and NA were transmitted most efficiently, those
with swine-like HA and NA were transmitted minimally or not transmitted, and those with swine-like
HA and human-like NA (N2) showed intermediate transmissibility.
------------------------------------------------------------------
Abstract
We previously reported that A/swine/Korea/1204/2009(H1N2) virus was virulent and transmissible in ferrets in which the respiratory droplet'transmissible virus (CT-Sw/1204) had acquired simultaneous HAD225G and NAS315N mutations. Incorporating these mutations into the non-pathogenic A/swine/Korea/1130/2009(H1N2, Sw/1130) virus consequently altered pathogenicity and growth in animal models but could not establish efficient transmission or remarkable disease. We, therefore, exploited various reassortants of these two viruses to better understand and identify other viral factors responsible for pathogenicity, transmissibility, or both. We found that possession of the CT-Sw/1204 tripartite viral polymerase enhanced replicative ability and pathogenicity in mice more significantly than did individual expression of polymerase subunit proteins. In ferrets, homologous expression of viral RNA polymerase complex genes in the context of the mutant Sw/1130 carrying the HA225G and NA315N modifications induced optimal replication in the upper nasal and lower respiratory tracts and also promoted efficient aerosol transmission to respiratory droplet'contact ferrets. These data show that the synergistic function of the tripartite polymerase gene complex of CT-Sw/1204 is critically important for virulence and transmission independent of the surface glycoproteins. Sequence comparison results reveal putative differences that are likely to be responsible for variation in disease. Our findings may help elucidate previously undefined viral factors that could expand the host range and disease severity induced by triple-reassortant swine viruses, including the A(H1N1)pdm09 virus, and therefore further justify the ongoing development of novel antiviral drugs targeting the viral polymerase complex subunits.


CT-Sw/1204 (=A/Sw/Korea/1204/2009(H1N2)+D225G(4)+S315N(6)
is virulent and transmissible in ferrets
segments 1,2,3 are responsible for enhanced replication and pathogenicity in mice
1,2,3 from Sw/1204 and 4,5,6,7,8 from A/Sw/Korea/1130/2009(H1N2) and D225G(4) and S315N(6)
was transmissible in ferrets
1130 and 1204 are triple reass.
-------------------------------------------------------------------------------------------
http://jvi.asm.org/content/83/16/8131.full.pdf
2005-2009 : H5N1(THA05+H3N2(WY05) , ferrets attenuated, not transmissible
 
Re: list of reassortment studies

http://www.sciencemag.org/content/early/2013/07/17/science.1240532
The viruses isolated from birds were nonpathogenic in chickens, ducks, and mice;
however, the viruses isolated from humans caused up to 30% body weight loss in mice.
Most importantly, one virus isolated from humans was highly transmissible in ferrets by
respiratory droplets.

Three human viruses (SH/1, SH/2, and AH/1)

and even though their HA and NA proteins were genetically quite similar, at least one H7N9
isolate transmitted readily via respiratory droplets among ferrets.

four of the five viruses tested could be transmitted between ferrets in direct contact with
each other, and one transmitted with high efficiency via respiratory droplets.

H7N9 in one ferret exposed to those infected with one of the bird strains and two human
strains isolated from some of the first patients in Shanghai

virus in all three ferrets exposed to animals with AH/1

mouse study: SH/1, SH/2, AH/1, CK/S1053, PG/S1069, PG/S1421

ferret transmission study: SH/1, SH/2, AH/1 ,CK/S1053 , PG/S1421

For the respiratory droplet transmission studies, groups of three ferrets were
inoculated i.n. with 106 EID50

-------------------------------------------------
amino-acid differences from the index:
SH/1:4,3,0,9,5,2,1,1
SH/2:2,0,0,0,0,1,0,0
AH/1:1,0,0,0,0,0,0,0
CK/S1053:0,0,0,0,0,6,1,0
PG/S1421:0,0,0,0,0,0,0,0

nucleotide-differences from the index:
SH/1:8,13,3,12,35,8,1,2
SH/2:3,1,0,1,0,1,0,0
AH/1:1,1,1,0,0,1,0,0
CK/S1053:2,1,0,3,0,8,1,0
PG/S1421:1,1,0,1,2,3,1,0
 
Re: list of reassortment studies

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3393695/ , July 2012
summary:
virulent mouse-adapted H9N2 (147L,627K) , 8 lung passages-->M147L(1),V250G,E627K,L226Q(4),R210K(7)
in A/chicken/Shandong/16/05(H9N2) [that virus is not at genbank,
Shandong however is in NE-China, so presumably quite different from the H9N2
that led to H7N9 (as are other H9N2 from Shandong)]
-----------------------------------------------------
more details and keywords:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3393695/

Increased virulence was detectable after 8 sequential lung passages in mice.
Five amino acid substitutions were found in the genome of SD16-MA compared
with SD16 virus: PB2 (M147L, V250G and E627K), HA (L226Q) and M1 (R210K).
[none of the avian viruses at genbank have L at 147 in PB2 : I=7410,M=82,T=966,V=236]

Assessments of replication in mice showed that all of the SD16-MA PB2, HA and M1
genome segments increased virus replication; however, only the mouse-adapted PB2
significantly increased virulence. Although the PB2 E627K amino acid substitution
enhanced viral polymerase activity and replication, none of the single mutations of
mouse adapted PB2 could confer increased virulence on the SD16 backbone.
The combination of M147L and E627K significantly enhanced viral replication ability
and virulence in mice. Thus, our results show that the combination of PB2 amino
acids at position 147 and 627 is critical for the increased pathogenicity of H9N2
influenza virus in mammalian host.

A/Chicken/Hebei/4/2008 virus caused acute respiratory distress syndrome (ARDS) in mice,

A mouse-adapted H9N2 virus, generated by serial lung-to-lung passage, gained improved
growth characteristics on mammalian cells, extended tissue tropism in mice, and was lethal for mice [17].

Isoleucine residue at position 97 in PA protein plays a key role in enhanced virulence in mice and is
implicated in the adaptation of avian influenza viruses to mammalian hosts [27].
-------------------------------------------------------------------------------

http://jvi.asm.org/content/early/2012/12/19/JVI.02688-12.full.pdf
http://jvi.asm.org/content/early/2012/12/19/JVI.02688-12.full.pdf
H9N2 influenza viruses with an A316S substitution in hemagglutinin (HA) and a
shorter neuraminidase (NA) stalk have become predominant in China. The A316S
was shown to increase HA cleavage efficiency when combining with short stalk NA,
and the short stalk NA improved NA enzyme activity and release of virus from
erythrocytes. Single or combination of these mutations strengthened the virulence of
H9N2 virus in chickens and mice.
-----------------------------------------------------------------------------------------
BJ/94-like lineage
1994–2004, 79.8–95.4% of Chinese H9N2 influenza viruses
possessed the PARSSR/GL amino acid sequence motif in the HA cleavage site



------------------
20. Sun, Y., J. Pu, Z. Jiang, T. Guan, Y. Xia, Q. Xu, L. Liu, B. Ma, F. Tian, E.
G. Brown, and J. Liu. 2010. Genotypic evolution and antigenic drift of H9N2
influenza viruses in China from 1994 to 2008. Vet Microbiol 146:215-225.
five series (BJ/94-, G1-, BG-, F/98- and Aq-series
BJ/94,F/98 in N and S China, others in S-China
BJ/94 <2000,F/98 since 2004
--------------
26. Xu, K. M., G. J. Smith, J. Bahl, L. Duan, H. Tai, D. Vijaykrishna, J. Wang,
J. X. Zhang, K. S. Li, X. H. Fan, R. G. Webster, H. Chen, J. S. Peiris, and
Y. Guan. 2007. The genesis and evolution of H9N2 influenza viruses in
poultry from southern China, 2000 to 2005. J Virol 81:10389-10401.
http://jvi.asm.org/content/81/19/10389.short
Chicken/Beijing/1/94 (Ck/Bei-like) and Quail/Hong Kong/G1/97 (G1-like)
Duck/Hong Kong/Y439/97 (Y439-like or Korean-like)
Qa/HK/G1/97, Dk/HK/Y280/97, and Ck/HK/G9/97,
A total of 89 H9N2 viruses were isolated from 49,150 duck samples
----------------------------------------------------------------------
 
Re: list of reassortment studies

http://mbio.asm.org/content/1/1/e00067-10.full

VN1203=V=A/Vietnam/1203/2004(H5N1)
CH58=C=A/Ck/Vietnam/C58/2004(H5N1)
CA09=M=A/California/04/2009(pH1N1)
NY312=N=A/New York/312/2001(H1N1)
S09=O=A/green winged teal/Ohio/175/1986(H2N1)
1918=8=A/Brevig Mission/1/1918(H1N1)

6=1918-K627E=68888888
E=NY-K627E=ENNNNNNN
K=S09-E627K=KOOOOOOO
CA09-E627K=XMMMMMMM
CA09-D701N=YMMMMMMM

rNY312=NY312=NNNNNNNN
rNY312-K27E=ENNNNNNN
1918RNP=888N8NNNN
1918RNP-K627E=688N8NNN
VN1203RNP=VVVNVNNN
S09RNP=OOONONNN
S09RNP-E627K=KOONONNN
CA09RNP=MMMNMNNN
CA09RNP-E627K=XMMNMNNN
CA09RNP-D701N=YMMNMNNN
=VVVCCCCC
=CCCVVVVV


TABLE 1
Characteristics of viruses evaluated in this study
Name,Genotype,Nadir weight-change (% of baseline),Lung titer (PFU/g) at 3dpi,at 5dpi, Histopathology
-----------------------------------------------------------------------------------------------------------------------------------------------
rNY312,NY312,−0.62%,2.6e3,2.7e3,fif+vrva
rNY312-K627E,NY312, PB2-K627E,−0.57%,4.1e3,3.5e3,fif+vrva
1918RNP,1918RNP:NY312,−15.9%,7.7e5,6.5e5,mmnb+abva
1918RNP-K627E,1918RNP;PB2-K627E;NY312,+0.54%,4.4e4,2.6e5,fif+mbva
VN1203RNP,VN1203RNP:NY312,−15.7%,4.2e5,2.6e3,mmnb+abva
S09RNP,S09RNP:NY312,−4.93%,5.2e4,1.4e2,fa+pava
S09RNP-E627K,S09RNP;PB2-E627K:NY312,−8.06%,9.9e5,2.3e5,mb+obva
CA09RNP,CA09RNP:NY312,−4.18%,2.2e5,4.1e4,mfnb+llobva
CA09RNP-E627K,CA09RNP;PB2-E627K:NY312,−0.83%,1.1e3,4.3e2,fif+vrva
CA09RNP-D701N,CA09RNP;PB2-D701N:NY312,−1.71%,1.2e4,2.5e3,fif,vrva

fif:Few inflammatory foci
vrva:very rare viral antigen
mmnb:Moderate-marked necrotizing bronchiolitis
abva:abundant bronchiolar viral antigen
mbva:minimal bronchiolar viral antigen
fa:Focal alveolitis
pava:predominantly alveolar viral antigen
mb:Mild bronchiolitis
obva:moderate bronchiolar viral antigen
mfnb:Mild, focal necrotizing bronchiolitis
llobva:low levels of bronchiolar viral antigen



------------add others to this table, add columns for MDCK,alveolar cells,ferret pathology,ferret transmission,humans
 
Re: list of reassortment studies

Viral RNA polymerase complex promotes optimal growth of 1918 virus in the lower respiratory
tract of ferrets , Kawaoka et.al. 2008
Substitution of single genes from the 1918 virus in the genetic background of
(A/Kawasaki/173/2001; K173) virus did not markedly alter the pattern of infection.
That is, the reassortants grew well in nasal turbinates, but only sporadically (if
at all) in the trachea and lungs. One exception was the 1918PB1/K173 reassortant,
which replicated efficiently in lung tissues as well as the upper respiratory tract.
A reassortant virus expressing the 1918 viral RNA polymerase complex (PA, PB1, and PB2)
and nucleoprotein showed virulence properties in the upper and lower
respiratory tracts of ferrets that closely resembled those of wild-
type 1918 virus. Our findings strongly implicate the viral RNA
polymerase complex as a major determinant of the pathogenicity
of the 1918 pandemic virus. This new insight may aid in identifying
virulence factors in future pandemic viruses that could be targeted
with antiviral compounds.
pathogenesis ? pandemic influenza


BKKKKKKK
KBKKKKKK lung
KKBKKKKK
KKKBKKKK
KKKKBKKK
KKKKKBKK
KKKKKKBK
KKKKKKKB
BBBKBKKK virulent in ferrets

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

Cited By ...

Viral RNA polymerase complex promotes optimal growth of 1918 virus in the lower respiratory tract of ferrets
Tokiko Watanabe, Shinji Watanabe, Kyoko Shinya, Jin Hyun Kim, Masato Hatta, Yoshihiro Kawaoka
Proc Natl Acad Sci U S A. 2009 January 13; 106(2): 588–592. Published online 2008 December 29. doi: 10.1073/pnas.0806959106
PMCID:
PMC2626747
Article PubReader PDF–877K Supplementary Material
Is Cited by the Following 24 Articles in this Archive:


Code: 
A (H1N1) pdm09 HA D222 variants associated with severity and mortality in patients during a second wave in Mexico
Reconstruction of the 1918 Influenza Virus: Unexpected Rewards from the Past
Analysis by Single-Gene Reassortment Demonstrates that the 1918 Influenza Virus Is Functionally Compatible with a Low-Pathogenicity Avian Influenza Virus in Mice
Engineering H5N1 avian influenza viruses to study human adaptation
Integrated Clinical, Pathologic, Virologic, and Transcriptomic Analysis of H5N1 Influenza Virus-Induced Viral Pneumonia in the Rhesus Macaque
Restored PB1-F2 in the 2009 Pandemic H1N1 Influenza Virus Has Minimal Effects in Swine
PB1-F2 Modulates Early Host Responses but Does Not Affect the Pathogenesis of H1N1 Seasonal Influenza Virus
Mutations in Polymerase Genes Enhanced the Virulence of 2009 Pandemic H1N1 Influenza Virus in Mice
Decoding the Distribution of Glycan Receptors for Human-Adapted Influenza A Viruses in Ferret Respiratory Tract
Autopsy series of 68 cases dying before and during the 1918 influenza pandemic peak
Insights on influenza pathogenesis from the grave
The pathogenesis of influenza virus infections: the contributions of virus and host factors
Pathogenesis of the 1918 Pandemic Influenza Virus
The contribution of animals models to the understanding of the host-range and virulence of influenza A viruses
PB2 Residue 158 Is a Pathogenic Determinant of Pandemic H1N1 and H5 Influenza A Viruses in Mice 
The HA and NS Genes of Human H5N1 Influenza A Virus Contribute to High Virulence in Ferrets
The PB2-E627K Mutation Attenuates Viruses Containing the 2009 H1N1 Influenza Pandemic Polymerase
MicroRNA Expression and Virulence in Pandemic Influenza Virus-Infected Mice 
Mechanisms and functional implications of the degradation of host RNA polymerase II in influenza virus infected cells
Attenuated Strains of Influenza A Viruses Do Not Induce Degradation of RNA Polymerase II 
Patterns of Oligonucleotide Sequences in Viral and Host Cell RNA Identify Mediators of the Host Innate Immune System
Emergence and pandemic potential of swine-origin H1N1 influenza virus
Nuclear Factor 90 Negatively Regulates Influenza Virus Replication by Interacting with Viral Nucleoprotein 
Adaptive Mutations Resulting in Enhanced Polymerase Activity Contribute to High Virulence of Influenza A Virus in Mice
 
Re: list of reassortment studies

http://www.ncbi.nlm.nih.gov/pubmed/24510170
February 2014 , Differences in transmissibility and pathogenicity of reassortants
between H9N2 and 2009 pandemic H1N1 influenza A viruses from humans and swine

a=A/Swine/Jiangsu/48/2010(pH1N1) [JS48]
b=A/Swine/Jiangsu/285/2010(pH1N1) [JS285]
9=A/Swine/Taizhou/5/08(H9N2-9.4.2.5) (TZ5)
1=A/California/04/2009(pH1N1) [CA04]

999a9999 ++tgp +pm
999b9999 ++tgp +pm
99919999 ++tgp +pm
999a9a99 +tgp +++pm
999b9b99 +tgp ++pm
99919199 +tgp ++pm

tgp:transmissibility in guinea pigs
pm:pathogenicity in mice
+:increased
------------------------------------------------------------
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An NA-deficient pH1N1 mutant can efficiently replicate in cultured cells
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