supplemental figure 1 - media.nature.com · supplemental figure 2 mock infb a549 (22 hpi) 20 40 60...

4
Supplemental Figure 1 40 80 120 0 0.000 0.041 0.123 0.370 1.111 3.333 10.000 30.000 ABT-199 (mM) 40 80 120 0 0.000 0.041 0.123 0.370 1.111 3.333 10.000 30.000 ABT-737 (mM) 40 80 120 0 0.000 0.041 0.123 0.370 1.111 3.333 10.000 30.000 ABT-263 (mM) 40 80 120 0 0.000 0.014 0.041 0.123 0.370 1.111 3.333 10.000 TW-37 (mM) RPE (24 hpi) RPE (24 hpi) RPE (24 hpi) RPE (60 hpi) RPE (60 hpi) 120 40 80 0 0.000 0.014 0.041 0.123 0.370 1.111 3.333 10.000 Gossypol (mM) DSS=21.4 DSS=66.1 DSS=55.6 DSS=0 DSS=0 Cell survival (%) Cell survival (%) Cell survival (%) Cell survival (%) Cell survival (%) N N NH SO 2 O NO 2 NH Cl O O N HN N N NH SO 2 O SO 2 CF 2 NH Cl S N O N N NH SO 2 O NO 2 NH Cl S N a TW-37 Gossypol OH H HO HO OH OH OH O O S HN OH HO HO O O O ABT-263 (mM) 40 80 120 0 0.000 0.014 0.041 0.123 0.370 1.111 3.333 10.000 DSS=58.77 b Mock IAV Cell survival (%) ABT-737 (mM) 40 80 120 0 0.000 0.014 0.041 0.123 0.370 1.111 3.333 10.000 Cell survival (%) ABT-199 (mM) 40 80 120 0 0.000 0.014 0.041 0.123 0.370 1.111 3.333 10.000 Cell survival (%) Gossypol (mM) 40 80 120 0 0.000 0.014 0.041 0.123 0.370 1.111 3.333 10.000 Cell survival (%) TW-37 (mM) 40 80 120 0 0.000 0.014 0.041 0.123 0.370 1.111 3.333 10.000 Cell survival (%) ABT-199 ABT-737 ABT-263 DSS=40.12 DSS=13.37 DSS=0 DSS=0 c Mock IAV Macrophages (11 hpi) Macrophages (11 hpi) Macrophages (11 hpi) Macrophages (11 hpi) Macrophages (11 hpi)

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Page 1: Supplemental Figure 1 - media.nature.com · Supplemental Figure 2 Mock InfB A549 (22 hpi) 20 40 60 80 100 120 0 0.000 0.014 0.041 0.123 0.370 1.1 1 1 3.33310.000 ABT-263 (mM) Mock

Supplemental Figure 1

40

80

120

0

0.00

0

0.04

1

0.12

3

0.37

0

1.11

1

3.33

3

10.0

00

30.0

00

ABT-199 (mM)

40

80

120

0

0.00

0

0.04

1

0.12

3

0.37

0

1.11

1

3.33

3

10.0

00

30.0

00

ABT-737 (mM)

40

80

120

0

0.00

0

0.04

1

0.12

3

0.37

0

1.11

1

3.33

3

10.0

00

30.0

00

ABT-263 (mM)

40

80

120

0

0.00

0

0.01

4

0.04

1

0.12

3

0.37

0

1.11

1

3.33

3

10.0

00

TW-37 (mM)

RPE (24 hpi)

RPE (24 hpi)

RPE (24 hpi)

RPE (60 hpi)

RPE (60 hpi)

120

40

80

0

0.00

0

0.01

4

0.04

1

0.12

3

0.37

0

1.11

1

3.33

3

10.0

00

Gossypol (mM)

DSS=21.4

DSS=66.1

DSS=55.6

DSS=0

DSS=0

Cell

surv

ival (

%)

Cell

surv

ival (

%)

Cell

surv

ival (

%)

Cell

surv

ival (

%)

Cell

surv

ival (

%)

ABT-263

ABT-199

ABT-737

N

N

NH

SO2

O

NO2

NH

Cl

O

ON

HN

N

N

NH

SO2

O

SO2CF2

NH

Cl

S

N

O

N

N

NH

SO2

O

NO2

NH

Cl

S

N

a

TW-37

Gossypol

OHH

HO

HOOH

OH

OHO

O

S

HN

OH

HO

HO

OO

O

ABT-263 (mM)

40

80

120

0

0.00

0

0.01

4

0.04

1

0.12

3

0.37

0

1.11

1

3.33

3

10.0

00

DSS=58.77

bMockIAV

Cell

surv

ival (

%)

ABT-737 (mM)

40

80

120

0

0.00

0

0.01

4

0.04

1

0.12

3

0.37

0

1.11

1

3.33

3

10.0

00

Cell

surv

ival (

%)

ABT-199 (mM)

40

80

120

0

0.00

0

0.01

4

0.04

1

0.12

3

0.37

0

1.11

1

3.33

3

10.0

00

Cell

surv

ival (

%)

Gossypol (mM)

40

80

120

0

0.00

0

0.01

4

0.04

1

0.12

3

0.37

0

1.11

1

3.33

3

10.0

00

Cell

surv

ival (

%)

TW-37 (mM)

40

80

120

0

0.00

0

0.01

4

0.04

1

0.12

3

0.37

0

1.11

1

3.33

3

10.0

00

Cell

surv

ival (

%)

ABT-199

ABT-737

ABT-263

DSS=40.12

DSS=13.37

DSS=0

DSS=0

cMockIAV

Macrophages (11 hpi)

Macrophages (11 hpi)

Macrophages (11 hpi)

Macrophages (11 hpi)

Macrophages (11 hpi)

Page 2: Supplemental Figure 1 - media.nature.com · Supplemental Figure 2 Mock InfB A549 (22 hpi) 20 40 60 80 100 120 0 0.000 0.014 0.041 0.123 0.370 1.1 1 1 3.33310.000 ABT-263 (mM) Mock

Supplemental Figure 2

MockInfB

A549 (22 hpi)

20

40

60

80

100

120

0

0.00

0

0.01

4

0.04

1

0.12

3

0.37

0

1.11

1

3.33

3

10.0

00

ABT-263 (mM)

MockEcho6

A549 (14 hpi)

20

40

60

80

100

120

0

0.00

0

0.01

4

0.04

1

0.12

3

0.37

0

1.11

1

3.33

3

10.0

00

ABT-263 (mM)

MockMeV

Vero (36 hpi)

20

40

60

80

100

120

0

0.00

0

0.01

4

0.04

1

0.12

3

0.37

0

1.11

1

3.33

3

10.0

00

ABT-263 (mM)

MockHSV-1

RPE (18 hpi)

20

40

60

80

100

120

0

0.00

0

0.01

4

0.04

1

0.12

3

0.37

0

1.11

1

3.33

3

10.0

00

ABT-263 (mM)

MockBUNV

BHK-21 (26 hpi)

20

40

60

80

100

120

0

0.00

0

0.01

4

0.04

1

0.12

3

0.37

0

1.11

1

3.33

3

10.0

00

ABT-263 (mM)

MockHSV-2

RPE (9 hpi)

20

40

60

80

100

120

0

0.00

0

0.01

4

0.04

1

0.12

3

0.37

0

1.11

1

3.33

3

10.0

00

ABT-263 (mM)

MockSINV

Vero (20 hpi)

20

40

60

80

100

120

0

0.00

0

0.01

4

0.04

1

0.12

3

0.37

0

1.11

1

3.33

3

10.0

00

ABT-263 (mM)

MockKSHV

iSLK.219 (23 hpi)

20

40

60

80

100

120

0

0.00

0

0.01

4

0.04

1

0.12

3

0.37

0

1.11

1

3.33

3

10.0

00

ABT-263 (mM)

MockSFV

Vero (12 hpi)

20

40

60

80

100

120

0

0.00

0

0.01

4

0.04

1

0.12

3

0.37

0

1.11

1

3.33

3

10.0

00

ABT-263 (mM)

MockVACV

RPE (24 hpi)

20

40

60

80

100

120

0

0.00

0

0.01

4

0.04

1

0.12

3

0.37

0

1.11

1

3.33

3

10.0

00

ABT-263 (mM)

MockDENV

Vero (45 hpi)

20

40

60

80

100

120

0

0.00

0

0.01

4

0.04

1

0.12

3

0.37

0

1.11

1

3.33

3

10.0

00

ABT-263 (mM)

MockTBEV

Vero (45 hpi)

20

40

60

80

100

120

0

0.00

0

0.01

4

0.04

1

0.12

3

0.37

0

1.11

1

3.33

3

10.0

00

ABT-263 (mM)

Cell

surv

ival (

%)

Cell

surv

ival (

%)

Cell

surv

ival (

%)

Cell

surv

ival (

%)

Cell

surv

ival (

%)

Cell

surv

ival (

%)

Cell

surv

ival (

%)

Cell

surv

ival (

%)

Cell

surv

ival (

%)

Cell

surv

ival (

%)

Cell

surv

ival (

%)

Cell

surv

ival (

%)

No virus Echo6

A549 (8 hpi)

No in

hib

itor

AB

T-2

63 (

1 m

M)

*

a b

Page 3: Supplemental Figure 1 - media.nature.com · Supplemental Figure 2 Mock InfB A549 (22 hpi) 20 40 60 80 100 120 0 0.000 0.014 0.041 0.123 0.370 1.1 1 1 3.33310.000 ABT-263 (mM) Mock

PB

2 m

RN

A

(copy

num

ber,

)

5x1

0-

NS

1 m

RN

A(c

opy

num

ber,

6

x10

-)

ß-a

ctin

mR

NA

(co

py

num

ber,

5

x10

-)

Time (h)

0

0,4

0,8

1,2

1,6

1 2 3 4 5 6 7 8 9

0

1

2

3

4

0

2

4

6

8

a

c

- NS1/M1

- NP

AB

T-2

63

- NS1/M1

- NP

No d

rug

- -actß

-NS1

2 4 6 8 10 12 14 16 18 20 22 24

- -actß

-NS1AB

T-2

63

No d

rug

2 4 6 8 10 12 14 16 18 20 22 24

Time (h)

b

Supplemental Figure 3

1 2 3 4 5 6 7 8 9

1 2 3 4 5 6 7 8 9

Time (h)

Time (h)

Time (h)

14

0

28

IAV:ABT-263:

- +- +

- +- +

Virus

titer

-3(P

FU

/ml,

x10

)

IAV

IAV, ABT-263

e

- +IAV:- +ABT-263:

- +- +

1h

- +- +

- +- +

2h

- +- +

- +- +

3h

- +- +

- +- +

6h

-

- -+

24h

25-

20-

15-

37-

50-

10-

-Bid

d

- -actß

Page 4: Supplemental Figure 1 - media.nature.com · Supplemental Figure 2 Mock InfB A549 (22 hpi) 20 40 60 80 100 120 0 0.000 0.014 0.041 0.123 0.370 1.1 1 1 3.33310.000 ABT-263 (mM) Mock

Supplemental Figure 4

IAV, ABT-263

IAV, ABT-737

IAV, ABT-199

IAV, gossypol

IAV, TW-37

C5aCD40

CSFbCSFa

CXCL1

CCL1CD54

IFNgRS RS

RS

NegC

IL1a IL1b IL2 IL4 IL5 IL6 IL8IL1raIL10 IL12 IL13 IL16 IL17 IL17E IL23 IL27IL32a IP10 ITAC CCL2 MIF CCL3 CCL4 PAI1

RANTESSDF1

TNFa

sTREM1

RANTES0

20

40

60

IL-60

20

40

60

80

100

IL-80

20

40

60

Rela

tive in

tensi

ty (

%)

CXCL20

20

40

60

80

100

120

IP-100

20

40

60

IL-1ra0

10

20

IAV, ABT-199IAV, gossypol

IAV, ABT-737IAV, ABT-263

IAV, TW-37IAV