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R a p i d c o m m u n i c a ti o n s

ORIGINS OF THE NEW INFLUENZA A(H1N1) V I R U S : T I M E TO


TA K E A C T I O N

G M Nava (gerardomnava@gmail.com)1,2, M S Attene-Ramos2, J K Ang2, M Escorcia1


1. Facultad de Medicina Veterinaria y Zootecnia (College of Veterinary Medicine), Universidad Nacional Autonoma de Mexico
(National Autonomous University of Mexico), Mexico City, Mexico
2. Institute for Genomic Biology, University of Illinois at Urbana-Champaign, United States

To gain insight into the possible origins of the 2009 outbreak of  +E""$Y"84#/
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72)!:5%::%4!$ 43$ %!&'"!()$ *?$ J>':$ 7>":"$ )!)89:":$ <4!72%K'7"$ 74$
7>"$"=%6"!<"$43$7>"$248"$43$1%;$141'8)7%4!:$):$M5%N%!;$="::"8:O$342$ Phylogenetic analysis
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Introduction 43$%!&'"!()$*+,-.-/$=%2':":$<%2<'8)7%!;$%!$.427>$*5"2%<)$342$7>"$
P!$ GA$ *12%80$ 7>"$ Q4286$ ,")87>$ P2;)!%()7%4!$ +Q,P/$ 2"8"):"6$ 8):7$7#4$6"<)6":$+3245$-HIH$74$GBBH/?$W247"%!$:"C'"!<":$3245$
7>"$R2:7$)8"27$%!6%<)7%!;$7>"$4<<'22"!<"$43$<4!R25"6$>'5)!$<):":$ )=%)!0$ :#%!"$ )!6$ >'5)!$ %!&'"!()$ =%2':":$ #"2"$ 4K7)%!"6$ 3245$
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Methods and results %!&'"!()$*+,-.-/$=%2':":$+@%;'2"$G/?$
Protein homology analysis
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%!&'"!()$=%2':":$7>)7$>)="$K""!$<%2<'8)7%!;$%!$7>"$X!%7"6$E7)7":$ %!7"2:1"<%":$72)!:5%::%4!$43$%!&'"!()$*$+2"1427"6$<):":$4<<'22"6$
)!6$*:%)$342$7>"$8):7$6"<)6"$+@%;'2"$-0$E'118"5"!7)29$5)7"2%)8:[$ %!$\4#)0$Z)298)!6$)!6$Q%:<4!:%!0$X!%7"6$E7)7":$K"7#""!$-HH-$)!6$
@%;'2"$-$)!6$J)K8"$-/?$ GBB_/$+@%;'2"$G0$E'118"5"!7)29$5)7"2%)8:[$@%;'2"$G$)!6$J)K8"$c/?$

@%;'2"$-?$W4::%K8"$42%;%!:$43$7>"$%!&'"!()$GBBH$*+,-.-/$=%2':[$ Discussion and conclusion


)/$>"5);;8'7%!%!$)!6$K/$!"'2)5%!%6):"$1247"%!:$ *87>4';>$ 8%5%7"6$ %!$ :)518"$ :%("0$ 4'2$ )!)89:":$ :'K:7)!7%)7"$
7>"$ =)8'"$ 43$ 548"<'8)2$ :<2""!%!;$ )!6$ 1>984;"!"7%<$ )::"::5"!7$

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2 E U R O SU R V E I L L A N C E Vol . 14 · I ss u e 22 · 4 J u n e 20 0 9 · w w w. e uro s u rve i ll an c e . o rg


This article was published on 4 June 2009.
Citation style for this article: Nava GM, Attene-Ramos MS, Ang JK, Escorcia M. Origins of
the new influenza A(H1N1) virus: time to take action. Euro Surveill. 2009;14(22):pii=19228.
Available online: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19228

E U RO S U R V E I L L A N C E Vol . 14 · I ss u e 22 · 4 J u n e 20 09 · w w w. e u ro s urve ill an ce . o rg 3


Figure 1. Possible origins of the influenza 2009 A(H1N1) virus: a) hemagglutinin and b) neuraminidase proteins

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Protein sequences from the 2009 A(H1N1) virus were retrieved and used for BLAST searches versus the all-species NCBInr protein database. Top-fifty best hits were retrieved from
GenBank and used for phylogenetic tree reconstruction using the maximum parsimony method. Phylogenetic trees were rooted using the earliest influenza virus found with the analysis.
Proteins from the 2009 A(H1N1) virus (red circles) showed close homology to proteins from swine influenza viruses circulating in Asia, Europe and US (blue circles) and swine influenza
viruses that have infected humans in recent past (red squares). Protein relationships with avian influenza virus (green circles) were more distant. Scale bar indicates the number of changes
over the whole sequence. Phylogenetic trees for PB2, PB1, PA, NP, MP1, and NS1 proteins, and details of statistical significance of branch order are provided in Supplementary Materials -
Figure 1.
Figure 2. Genetic distinctness of the influenza 2009 A(H1N1) virus: a) hemagglutinin (HA) and b) neuraminidase (NA)
proteins; c) phylogenetic trees for PB2, PB1, PA, NP, MP1, and NS1 proteins

a! HA b NA
Mixing!vessel

2009!A(H1N1)

Genetic!
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5 5 5

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1 5
Legend:
a) and b)
Protein sequences from avian, swine and human influenza A(H1N1) viruses circulating in North
America from 1989 to 2009 were retrieved from the Influenza Virus Resource. Sequences were
used for the reconstruction of unrooted phylogenetic trees with the maximum parsimony method.
Proteins from the influenza 2009 A(H1N1) virus (red triangles), earlier human (red and pink
circles) swine (navy blue and purple circles) and avian (green circles) viruses are shown. Light
colors (pink, purple and green) correspond to viruses found between 1989 and 1999 and dark
(red, navy blue and green) colors to viruses found between 2000 and 2009. Arrow indicates the
influenza swine cluster containing an assortment of avian and human viruses. Genetic
distinctness between pig-human interspecies transmission of influenza A viruses (orange squares;
cases occurred in Iowa, Maryland and Wisconsin, US between 1991 and 2006) and the main
cluster of human influenza viruses are indicated with the left bracket. Similar noticeable
phylogenetic differences are observed between the influenza 2009 A(H1N1) virus and the main
human influenza virus cluster. Scale bar indicates the number of changes over the whole
sequence.
c)
Detailed phylogenetic tree topology, protein accession numbers, virus strains and serotypes, and
statistical significance of branch order are presented in Supplementary Materials - Figure 1.
Supplementary Fig. 1. Possible origins of influenza 2009 A(H1N1) virus. a, PB2; b, PB1 and
c, PA polymerases; d, hemagglutinin; e, nucleocapsid protein; f, neuraminidase; g, matrix
protein 1; h, nonstructural protein 1. Protein sequences from the 2009 A(H1N1) virus were
used for BLAST searches versus the all-species NCBInr protein database. Top fifty best hits
were retrieved from GenBank and used for phylogenetic tree reconstruction using the
maximum
i parsimony
i method.
h d Phylogenetic
Ph l i trees were constructedd with
i h the
h maximum
i
parsimony method using the MEGA software version 4.0 and rooted using the earliest
influenza virus isolates obtained with the analyses. The statistical significance of branch order
was estimated by the generation of 100 replications of bootstrap resampling of the originally-
aligned amino acid sequences.
sequences Scale bar indicates the number of changes over the whole
sequence.

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9
Supplementary Fig. 2. Genetic distinctness of the influenza 2009 A(H1N1) virus. a, PB2; b,
PB1 and c, PA polymerases; d, hemagglutinin (HA); e, nucleocapsid protein (NP); f,
neuraminidase (NA); g, matrix protein 1 (MP1); h, nonstructural protein 1 (NS1). Protein
sequences from avian, swine and human influenza A (H1N1) viruses circulating in North-
America from 1989 to 2009 were retrieved from the Influenza Virus Resource. Sequences were
usedd for
f unrootedd phylogenetic
h l i tree construction
i with
i h the
h maximum
i parsimony
i method.
h d
Proteins from the influenza 2009 A(H1N1) virus (red triangles), earlier human (red and pink
circles) swine (navy blue and purple circles) and avian (green circles) viruses are shown. Light
colors (pink, purple and green) correspond to viruses found between 1989 and 1999 and dark
colors (red,
(red navy blue and green) to viruses found between 2000 and 2009.
2009 Orange squares
represent pig-human interspecies transmission of influenza A cases occurred in Iowa,
Maryland and Wisconsin, USA between 1991 and 2006. Scale bar indicates the number of
changes over the whole sequence. Phylogenetic trees were constructed with the MEGA
software version 4.0. The statistical significance of branch order was estimated by the
generation of 100 replications of bootstrap resampling of the originally-aligned amino acid
sequences. Scale bar indicates the number of changes over the whole sequence.

10
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