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Lmerg|ng v|ruses

LecLure 23
8lology W3310/4310
vlrology
Sprlng 2013
!"#$%&' )&*+,)- .+# /$0&')1
PL8ACLl1uS
1
Lmerg|ng v|ruses
-
23),'%&' 4%,+- - causauve agenL of a new or prevlously
unrecognlzed lnfecuon
-
1he Lerm became popular ln 1990s, buL emerglng
vlruses are noL new
-
Slnce Lhe rlse of agrlculLure - 11,000 years ago - new
lnfecuous agenLs have lnvaded human populauons
because Lhey can be susLalned by numbers LhaL were
unknown before agrlculLure and commerce
2
Lmerg|ng v|ruses
-
Lxpanded hosL range wlLh an lncrease ln dlsease noL
prevlously obvlous
-
1ransmlsslon of a vlrus from a wlld or domesucaLed
anlmal Lo humans - 5""&"-%-
-
Cross-specles lnfecuon may esLabllsh a new vlrus ln
Lhe populauon (Slv movlng from chlmps Lo humans)
-
Cen cross-specles lnfecuon cannoL be susLalned
(e.g. Lbola and Marburg from baLs Lo humans)
3
4
S|x factors that dr|ve v|ra| emergence
rlnclples of vlrology, ASM ress
5
Cver-r|d|ng factors
dr|v|ng the emergence of
|nfecnous d|seases of humans and an|ma|s:
6+30& 7"7+809"& ',":#$ 0&* %&/,)*%.8)
/$0&') "//+,,%&' %& 088 )/"-;-#)3- .,"+'$#
0."+# .; $+30& "//+709"& "< 083"-# )4),;
/",&), "< #$) 780&)#
Nanona| Geograph|c Soc|ety
!"#$% ' (#$) *#+"$,
-%**./ ' 01$231* +1, 4230.5
6%7 ' 83%,
6
Convergent Iorces of D|sease Lmergence

DLICkLS1A1ICN

LkANDING
CULA1ICNS
"MLGA- CI1ILS"
CVLk1
GLC8ALI2A1ICN
kAID AIk 1kAVLL

LNVIkCNMLN1AL CnANGLS
AL1LkLD
LCCSS1LMS

MICkC8IAL
LVCLU1ICN
7
G|oba| av|anon network
8
ko|es of Lvo|unon
Leads Lo Lhe blodlverslLy of paLhogens exlsung ln
naLure
AdapLauon Lo new hosLs and envlronmenLs
(Lhrough varlauon and selecuon)
9
1he Amazon North keg|on of 8raz||
6"3) #" =>? @,#$,"7"*A.",&) 0&* B#$), C),#).,0#) C%,+-)-
Acre
Rondonia
Amazonas
Para
Tocantins
Amapa
Roraima
Porto Velho
Manaus
Belem
Macapa
Palmas
Rio Branco
0
Boa Vista
Aura, EEE, Una, WEE, Bussuquara, Ilheus,
Kairi, Maguari, Taiassui, Caraparu, Itaqui,
Murutucu, Nepuyo, Melao, Acara, Benevides,
Benfica, Bushbush, Capim, Guajara,
Ananindeua, Bimiti, Catu, Mirim, Moju,
Timboteua, Utinga, Turlock, Bujaru, Icoaraci,
Itaporanga, Urucuri, Belem, Para, Acado-like,
Mosqueiro, Kwatta-like, Chaco, Timbo, Piry,
Marco, Aruac, Inhangapi, Agua Preta, Cotia-
like, Marajo, Mucambo, yellow fever,
Tacaiuma, Tucunduba, Apeu, Marituba,
Oriboca, Caraparu-like, Guama, Anhanga,
Mayaro
Pixuna, SLE, Lukuni, Sororoca, Guaroa,
Oropouche, Candiru, Pacui, Caninde,
Gurupi, Irituia, Ourem, Tembe, Cocal,
Jurona
Cacipacore, Trombetas, Mapuera,
Oriximina, Turuna, Saraca, Juruaca
Arumateua, Caraipe,Tucurui,Guamboa-Like,
Uriurana, Anapu, Aracai, Aratau, Aruana, Arawete,
Bacuri, Canoal, Coari, Iopaka, Ipixaia, Iruana,
Itaboca, Jandia, Jatuarana, Pacaja, Parakana,
Paranati, Pependana, Pindobai, Piratuba, Surumbi,
Tekupeu, Timbozal, Tocantins, Tocaxa, Tuere,
Xaraira, Xiwanga, Breu Branco, Trocara, Jatobal,
Jacunda.
Xingu, Ambe, Joa, Tapara,
Acatinga, Acurene, Altamira,
Assurinis, Bacajai, Gorotire,
Kararao, Uxituba, Cajazeira,
Codajas, Galibi, Iriri, Uruara
Itaituba, Pacora-
like,
Jacareacanga,
Flexal
Santarem,
Jamanxi
dengue 2, dengue 3,
Bocas, Triniti,
Barcarena
Murumbi
Munguba, Jari, Jutai,
Monte Dourado, Paru,
Tumucumaque, Almeirim
Serra Norte, Catete,
Parauapebas, Serra
Sul, Tapirope,
Carajas, Maraba,
Curianopolis,
Itacaiunas
Itupiranga
Melgaco
Mojui dos
Campos,
Belterra,
Cuiaba,
Alenquer
Serra do Navio,
Araguari, Amapari,
Ieri, Cupixi
dengue 1, dengue 4
Iaco, Moriche,
Purus, Sena
Madureira,
Xiburema
Ariquemes
Balbina,
Uatuma
North Region
A
t
la
n
t
ic
O
c
e
a
n
Atlantic Ocean
0 300 1,000
kllomeLers

Brazil
South America
SlLes from whlch vlruses were lsolaLed aL Lhe
Lvandro Chagas lnsuLuLe
10
rlnclples of vlrology, ASM ress
11
1he genera| |nteracnons of hosts and v|ruses
-
SLable: malnLalns vlrus ln ecosysLem
-
Lvolvlng: passage of vlrus Lo nalve populauon
-
uead-end: one way Lo dlerenL specles
-
8eslsLanL hosL: lnfecuon blocked
rlnclples of vlrology, ASM ress
12
Stab|e host-v|rus |nteracnons
-
8oLh paruclpanLs survlve and muluply
-
Some are eecuvely permanenL
A
6+30&- 0,) -"8) &0#+,08 $"-# <", 3)0-8)- 4%,+-D $),7)-
-%378)E 4%,+-D 6FGCD -30887"E
-
May lnclude lnfecuon of more Lhan one specles
A
H&I+)&50 @ 4%,+-D I04%4%,+-)-D #"'04%,+-)-
rlnclples of vlrology, ASM ress
13
Lvo|v|ng host-v|rus re|anonsh|p
-
Pallmarks are lnsLablllLy and unpredlcLablllLy
-
CuLcome of lnfecuon may range from benlgn Lo deaLh
-
lnLroducuon of smallpox and measles Lo nauves of Amerlcas
by Cld World colonlsLs and slave Lraders
-
lnLroducuon of WesL nlle vlrus lnLo WesLern Pemlsphere,
1999
-
vlrus may acqulre new properLy LhaL lncreases
vlrulence or spread, or lf hosL changes (e.g. famlne or
populauon change durlng wars)
rlnclples of vlrology, ASM ress
14
Dead-end |nteracnon
-
lrequenL ouLcome of cross-specles lnfecuon, buL noL
of lnLraspecles lnfecuons
-
Cen hosL ls kllled so qulckly LhaL Lhere ls llule or no
Lransmlsslon Lo oLhers
-
AlLernauvely, Lhe new lnfecLed hosL cannoL LransmlL
Lhe lnfecuon Lo oLhers of Lhe same specles
-
ConLrlbuLe llule Lo Lhe spread of a naLural lnfecuon
rlnclples of vlrology, ASM ress
15
1he comp|ex ||fe cyc|e of
an arbov|rus
SLable hosL-
vlrus lnLeracuons
rlnclples of vlrology, ASM ress
16
kodents and Insect Vectors Move Luropean
1|ck-borne Lncepha||ns Among Many nosts
Dead-end hosts
rlnclples of vlrology, ASM ress
17
Cther dead-end |nfecnons
-
?ellow fever (monkey)
-
Marburg, Lbola, Pendra, nlpah, SA8S progenlLor
(baLs)
-
Lassa, !unln, Sln nombre (rodenLs)
-
LaboraLory anlmal models
18
Lmerg|ng |nfecnons: 1wo steps
-
lnLroducuon
-
LsLabllshmenL and dlssemlnauon
19
Lncounter|ng new hosts
-
8are chance encounLers of vlruses wlLh new hosLs
may never be deLecLed
-
Slngle-hosL lnfecuons are noL Lransmlued among
humans for many reasons
20
Lxpand|ng v|ra| n|ches
-
Successful encounLers requlre access Lo suscepuble
and permlsslve cells
-
opulauon denslLy and healLh are lmporLanL facLors
-
vlrus populauons wlll survlve ln naLure only because
of -),%08 %&<)/9"&- (a chaln of Lransmlsslon)
21
numan are constant|y prov|d|ng new ways to
meet v|ruses
rlnclples of vlrology, ASM ress
22
rlnclples of vlrology, ASM ress
23
8ats: a source of zoononc
|nfecnons
-
lour prevlously unknown
paramyxovlruses lsolaLed from ylng foxes
slnce 1993, lncludlng nlpah and Pendra
vlruses
-
1hree cause severe dlsease ln domesuc
anlmals (horses and plgs) and are known
Lo lnfecL humans
24
N|pah v|rus
-
llrsL ouLbreak Malaysla 1998
A
B+#.,)0J "< ,)-7%,0#",; 0&* &)+,"8"'%/08 *%-)0-) "& 7%'
<0,3-
A
=KL $+30& *)0#$-D = 3%88%"& 7%'- /+88)*
-
lrulL baLs excreLe vlrus ln urlne buL are unaecLed
-
lg farmers planL mangoes near plgpens
-
lgs spread lnfecuon Lo humans
-
SubsequenLly humans lnfecLed by consumlng daLe palm sap
conLamlnaLed by baLs (lndla, 8engladesh)
-
Puman Lo human Lransmlsslon, lnfecuons conunue
25
nendra v|rus
-
ulscovered ln Pendra, AusLralla, SepLember 1994
A
B+#.,)0J J%88)* =M ,0/)$",-)- 0&* 0 #,0%&),
-
Spread from ylng foxes Lo horses, Lhen Lo humans
-
Porses conunue Lo acqulre lnfecuon
26
27
D|seases of exp|oranon and co|on|zanon
-
Lxploslve epldemlc spread may occur when a vlrus
enLers a nalve populauon
-
Smallpox reached Lurope from Lhe lar LasL ln 710 Au,
aualned epldemlc proporuons
-
Smallpox changed Lhe balance of human populauons
ln Lhe new World - kllled 3.3 mllllon AzLecs ln 2 years
(1320 - spread from Plspanlola), allowlng conquesL by
CorLez
28
e||ow fever v|rus: numans change the pauern
and pay the pr|ce
?ellow fever deaLhs,
hlladelphla, 1793
rlnclples of vlrology, ASM ress
N)88": O)4), :%88 *%-/"+,0') #$) ',":#$ "<
',)0# /%9)- %& "+, &09"&"
1PCMAS !LllL8SCn, 1800
29
Changes |n human popu|anons and env|ronments
-
Lmergence of epldemlc pollomyellus ln Lhe beglnnlng
of Lhe 20Lh cenLury: lmproved sanlLauon delayed
Lransmlsslon
-
known slnce 4,000 years ago, sLable hosL-vlrus
relauonshlp
30
o||omye||ns: A d|sease of modern san|tanon
rlnclples of vlrology, ASM ress
31
Chang|ng c||mate and an|ma| popu|anons
-
PanLavlrus pulmonary syndrome - rsL noLed ln Lhe lour
Corners area of new Mexlco, 1993
-
ulsease ls caused by Sln nombre vlrus, endemlc ln Lhe deer
mouse (P),"3;-/+- 30&%/+80#+-D 30 vlrus posluve)
-
Crlglnally called MuerLo Canyon vlrus, buL resldenLs
ob[ecLed Lo Lhe name
32
Chang|ng c||mate and an|ma| popu|anons
-
ln 1992-93, abundanL ralnfall produced a large crop of
plnon nuLs, food for humans and Lhe deer mouse. Mouse
populauon rose, conLacL wlLh humans lncreased.
-
1he vlrus ls excreLed ln mouse dropplngs, and
conLamlnaLed blankeLs or dusL from oors provlded
opporLunlues for human lnfecuon
-
Pumans are noL Lhe naLural hosL for Sln nombre vlrus, Lhe
human dlsease ls rare
-
noL new - earllesL known case 1939
33
D|str|bunon of 9%3.:),(2, :10#(2*1$2, and Locanon of nS
Cases as of August 27, 2003
1ota| Cases (N=349 |n 31 States)
9%3.:),(2,
:10#(2*1$2,
SNV
Cther v|rus
34
35
S|n Nombre
P),"3;-/+- 30&%/+80#+-
k|o Segundo
Q)%#$,"*"&#"3;- 3)E%/0&+-
L| Moro Canyon
Q)%#$,"*"&#"3;- 3)'08"9-
Andes
B8%'",;5"3;- 8"&'%/0+*0#+-
8ayou
B,;5"3;- 708+-#,%-
8|ack Creek Cana|
R%'3"*"& $%-7%*+-
k|o Mamore
B8%'",;5"3;- 3%/,"9-
Laguna Negra
F08"3;- 80+/$0
Mu|eshoe
R%'3"*"& $%-7%*+-
New ork
P),"3;-/+- 8)+/"7+-
Iuqu|nba
unknown PosL
Mac|e|
!)/,"3;- .)&)<0/#+-
nu39694
unknown PosL
Lech|guanas
B8%'",;5"3;- I04)-/)&-
ergam|no
@J"*"& 050,0)
Crn
B8%'",;5"3;- 8"&'%/0+*0#+-
Cao De|gad|to
R%'3"*"& 08-#"&%
Is|a V|sta
G%/,"#+- /08%<",&%/+-
8|ood|and Lake
G%/,"#+- "/$,"'0-#),
rospect n|||
G%/,"#+- 7)&&-;840&%/+-
8erme[o
B8%'",;5"3;- /$0/")&-%-
Ca|abazo
S;'"*"&#"3;- .,)4%/0+*0
Choc|o
B8%'",;5"3;- <+84)-/)&-
(V|rus Names |n Crange are Assoc|ated w|th numan D|sease)
New Wor|d nantav|ruses
36
nantav|rus zoononc |nfecnon |s a warn|ng that
potenna| human d|seases |urk |n the w||d |f we
|nadvertent|y |ntrude upon another host-paras|te
re|anonsh|p
37
SAkS - k|se and fa|| of a zoononc |nfecnon
nLuMCnlA - CPlnA (CuAnCuCnC): 8ll
**********************************
A roMLu-mall posL
<hup://www.promedmall.org>
roMLu-mall ls a program of Lhe lnLernauonal SocleLy for lnfecuous ulseases <hup://
www.lsld.org>
[1]
uaLe: 10 leb 2003
lrom: SLephen C. Cunnlon, Mu, hu, MP <cunnlon[erols.com>
1hls mornlng l recelved Lhls e-mall and Lhen searched your archlves and found noLhlng LhaL
perLalned Lo lL. uoes anyone know anyLhlng abouL Lhls problem?
"Pave you heard of an epldemlc ln Cuangzhou? An acqualnLance of mlne from a Leacher's chaL
room llves Lhere and reporLs LhaL Lhe hosplLals Lhere have been closed and people are dylng.
--
SLephen C. Cunnlon, Mu, hu, MP
lnLernauonal ConsulLanLs ln PealLh, lnc
Member AS1M&P, lS1M
<cunnlon[erols.com>
38
SAkS
-
CuLbreak of severe aLyplcal pneumonla, unknown
euology, Cuangdong rovlnce, Chlna, nov 2002
A
?KL /0-)-D L *)0#$-
-
lncubauon perlod 2-10 days
-
lllness beglns wlLh prodrome of fever
A
F$%88-D $)0*0/$)D 3080%-)D 3;08'%0
-
nexL phase: dry cough, shorLness of breaLh
-
10-20 may requlre mechanlcal venulauon
39
SAkS (Severe acute resp|ratory
syndrome)
-
A Chlnese docLor who LreaLed rsL pauenLs Lraveled
Lo Pong kong on 21 lebruary 2003, sLayed on nlnLh
oor of MeLropole PoLel
-
Pe dled ln hosplLal 22 lebruary
-
lnfecuon spread Lo 10 people ln hoLel, who ew Lo
Slngapore, vleLnam, Canada, uS before sympLoms
evldenL
-
lnfecuon spread Lo 8000 people ln 29 counLrles, 10
morLallLy
40
note| M
nong kong
Guangdong
rov|nce, Ch|na
A
A
n,I
A
n,I
nong kong SAk
nosp. 1: 99 nC
8 hosp|ta|s tota|
1ota|: 1S6 c|ose contacts of
nCW and panents
Un|ted States
1 nCW
I, L,M
I,L,M
k
Ire|and
0 nCW
k
S|ngapore
34 nCW
37 c|ose contacts
C,D,L
C,D,L
8
8
V|etnam
37 nCW
21 c|ose contacts
I,G
Canada
18 nCW
I,G
11 c|ose contacts
Spread from note| Metropo|e
(21 Iebruary 2003)
249 cases traced to "A" as of March 28, 2003
41
SA8S vlrlon
~120 nm
42
SAkS-CoV d|sease mechan|sms
-
1ransmlued by resplraLory
dropleLs
-
vlrus enLers resplraLory LracL and
muluplles ln eplLhellal cells
-
Mulupllcauon ln alveolar
eplLhellal cells leads Lo lung ln[ury
-
lmmune suppresslon cause of
severe dlsease?
rlnclples of vlrology, ASM ress
43
robab|e cases of SAkS by date of onset,
nong kong: n = 1 7S3, as of 9 Iune 2003
n
u
m
b
e
r

o
f

c
a
s
e
s
0
1 Ieb 13 Ieb 2S Ieb 9 Mar 21 Mar 2 Apr 14 Apr 26 Apr 8 May 20 May 1 Iun 9 Iun
0
20
40
60
80
100
120
CuLbreak ends !uly 2003
44
robab|e SAkS Cases Wor|dw|de
keported to WnC as of Sept. 26, 2003
Ch|na (S327)
S|ngapore (238 + 1)
nong kong (17SS)
V|etnam (63)
Canada (2S1)
U.S. (29)
Lurope:
10 countr|es (34)
1ha||and (9)
1a|wan (346)
1ota|: 8,098 cases, 774 deaths (9.6 case fata||ty)
Austra||a (6)
45
SAkS and the economy:
|mpact on g|oba| trave|
46
A|rport screen|ng and hea|th |nformanon,
nong kong, SAkS, 2003
47
ub||c nea|th kesponses to SAkS
-
Lpl Survelllance and early warnlng
-
Case lnvesugauon, conLacL Lraclng
-
lnLervenuons
-
lmmunlzauon: nC1 AvAlLA8LL
-
Anuvlral agenLs: nC1 AvAlLA8LL
-
1ravel resLrlcuons, quaranune: WluLL? uSLu
-
ubllc educauon
-
lnfecuon conLrol for healLhcare provlders and ln healLhcare
semngs
48
Cr|g|n of SAkS-CoV
-
Puman sera collecLed
before SA8S ouLbreak do
noL conLaln anubodles
Lo SA8S-Cov
-
Larly Cuangdong SA8S
cases were ln handlers
of anlmals for Lhe exouc
food markeL
-
Anlmal Lraders had
slgnlcanLly hlgher
prevalence of anu-SA8S-
Cov anubodles Lhan
conLrol groups
49
Annbody to coronav|rus |n humans, Guandong
rov|nce
Cccupanon # Annbody ()
Wlld anlmal Lrader 20 8 (40)
Anlmal slaughLerer 13 3 (20)
vegeLable handler 20 1 (3)
ConLrol
(hosp., non-resp.)
60 0 (0)
50
Cr|g|n of SAkS-CoV
-
vlrus lsolaLed from Plmalayan palm clveLs
ln llve-anlmal markeL ln Cuangdong (May
2003)
-
Lvldence LhaL some SA8S lnfecuons ln Chlna
were Lransmlued from clveLs Lo humans
-
ClveL culllng and quaranune lmposed
-
robably noL anlmal reservolr of Lhe vlrus:
!
ClveL vlruses >99.6 ldenuLy
!
vlrus noL oen lsolaLed from farm or wlld
clveLs
P0'+30 80,40#0 (alm clveL)
Llnk Lo humans?
51
Cr|g|n of SAkS-CoV
-
SA8S-llke Covs lsolaLed from dlerenL specles of horseshoe
baLs ln dlerenL reglons of Chlna
-
lsolaLed from provlnces >1000 km aparL
-
up Lo 84 of baLs examlned had anu-SA8S-Cov anubodles
-
8aL SA8S-llke-Covs 88-92 sequence ldenuLy wlLh human or
clveL sLralns
-
CreaLer geneuc dlverslLy ln baL vlruses Lhan Lhose of humans
or clveLs
-
PypoLhesls: baLs are reservolr of SA8S-Cov, Lransmlued Lo
humans vla markeL anlmals (e.g. clveLs)
52
now d|d SAkS-CoV adapt to humans?
-
Pundreds of SA8S vlral 8nA genomes were sequenced from
humans and anlmals durlng and aer Lhe epldemlc
-
Cov splke glycoproLeln ls a ma[or deLermlnanL of specles
speclclLy of lnfecuon
-
Puman and clveL sLralns dler by only four amlno aclds ln Lhe
recepLor-blndlng domaln, buL cause >1000-fold dlerence ln
blndlng amnlLy Lo cell recepLor, human angloLensln-converung
enzyme 2 (ACL2)
53
SAkS-Cov - ACL2 |nteracnon
large blndlng
lnLerface
addluon of
charge
deleuon of
meLhyl
pro reduces
blndlng
surface
large glycan
lacks
hydrophoblc
pockeL
54
W||| SAkS keturn?
-
no known Lransmlsslon of human SA8S-Cov. MosL recenL
human cases of SA8S-Cov lnfecuon were laboraLory-acqulred
(Chlna, Aprll 2004)
-
uecember 2003 - !anuary 2004: 4 SA8S cases ln Cuangdong
rovlnce, new anlmal - human Lransmlsslon
-
SA8S-Cov precursor conunues Lo clrculaLe ln anlmals, wlld
game banned ln markeLs
-
8e-emergence wlll be more qulckly recognlzed and conLalned
C8Lul1: MlCPALL 8L?nCLuS/LA/nLWSCCM
55
CoV-LMC
-
17 cases, 11 faLallues,
March 2013
-
Closely relaLed Lo baL
coronavlruses
-
noL SA8S-Cov
-
vlrus clrculaung ln Arablan
penlnsula
-
8lnds dlpepudyl pepudase
4 recepLor
Sclence 3 Aprll 2013: vol. 340 no. 6128 pp. 17-18
56
vlrus ulsease
PCov-229L
PCov-nL63
PCov-CC43
PCov-Pku1
SA8S-Cov
-
8esplraLory dlseases
- lebrlle upper LracL lnfecuon
- Lower LracL lnfecuons
- AsLhma exacerbauon
- ALyplcal pneumonla
Coronav|rus d|sease |n humans
1890, bovlne Cov
1686 - 1800, baL Cov
1430 - 1191, baL Cov
Cov-LMC
- Severe pneumonla
2003, baL Cov
57
Can|ne parvov|rus: Cat-to-dog by two mutanons
-
Canlne parvovlrus ldenued ln 1978, cause of new
enLerlc and myocardlal lnfecuon ln dogs
-
Lvolved from fellne panleukopenla vlrus, anoLher
parvovlrus
A
H&<)/#- /0#D 3%&JD ,0/""&
58
Can|ne parvov|rus
#:" 03%&" 0/%* /$0&')-T
59
now common are host range [umps?
-
uead end: very common
-
1hose LhaL produce susLalnlng Lransmlsslon: 8are
-
Can we predlcL Lhem? no
-
8uL we can know whaL ls ouL Lhere, and reacL
(preparedness)
60
Lmerg|ng |nfecnons can be detected and
contro||ed on|y by soc|enes w||||ng to pay
-
8esearch and developmenL ln academla and lndusLry
-
Larly deLecuon and ldenucauon Lechnology
-
uaLabases of all vlral genomes ln Lhe ecosysLem
-
llrsL responder acuons comblned wlLh rapld
communlcauon
-
ubllc healLh acuon lncludlng vacclnes, drug
sLockplles, quaranunes
-
lnLer-agency communlcauon and cooperauon among
local, sLaLe, and federal governmenL
61

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