ABCDEFG)HI)JKLIMDEFGN$"%&?@ABCD
EFGHIJK*LMNOPQRRRS!"#$"%&'()'*+,-.%/0123*456789:;<=#>-TUVW;HIXYZK$"%&RRRS[\?]^_`LabcDdef`gh?ijD_Pk0
HlmnKodpXqrKseXPtu_ftvS!"#$%$"%&'()'*+,?wxcD&'()*+),-.
/0123,-4567/089:;#<=>)?@

ayRz{?|f}~•cD!"#$"%&LRRR.%!"#$"%&!€©‚ƒ„!LRRRš›PHœ5X78_†‡ˆd‰ŠJK“'k•žK*c12!"#$"%&!€•‚ƒ„!L…12X78_†‡ˆd‰ŠJKS

12!"#L…©‚ƒk123456789:_…12¬G®¯_v°±…²l³“´Zvµ¶GQKS©‚ƒ!L…12X78JK“'kGlKS•‚ƒL…‹VŒV•Ž••‘’W%X78JK“'kGlKS©‚ƒL….%5ª«X78JKRRR ¸¹GLP™S'“”k…•‚ƒL•<–W%•<=—"W%X78JK˜kGlP™S
Ÿ5*¡^_`LŸ2¢£#>?$"%&¤¥ˆD¡k•¦JKc.%5-X·™u^Ÿ56*¡k•¦JKc•‚ƒLŸ()§¡*¨™$"%&GQK/^_ZP™RRRS!"#$"%&*[\-×ØÙÚ©‚ƒ*.%Ê¾6fvL4¾678*ÕÖ
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©‚ƒº»¼?½»¼»¼»¾D<=()*56NefTatPIC'./0

ËÌÍW%Gag&'•ÎÏ<ÐÑÏW%Transact iv

a tionRevDouble spliced1232)*'4/0
Non-spliced
Single spliced

1!"#$"%&'ÛÜÝhJK()ÞCß
•‚ƒ78àá.%ÞCâ!ãä‚½å»æÄÇ»*ç•‚ƒÝhÙè

G@HIJ!"#$%+,K&'>?@ABCDEFC
()*

'1232

A. L. Brass et al., Science 319, 921 (2008)

HIV-1
H9

Vif (Virion Infectivity Factor)

2000

rev
tat
gag

HIV-1 Vif(-)
nef

vpu

vif
pol

env

vpr

LTR

RT activity (cpm)

LTR

1500

30000

1000

20000

500

10000

HIV-1 Vif(-)
Vif(-)

00246810

rev

gag

1421646810121416nefvpuvifpol

12Days after infection

tatLTRJurkat
40000

HIV-1env

vpr

LTR

Apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3 (APOBEC3G, 3F),
the newly identified target of HIV-1 Vif, represents an endogenous inhibitor of HIV-1 replication.

•‚ƒìíîà12ÞCÒÄÃïð*ç$"%&*ç$"%&ÝhÙèÝhÙè•‚ƒìíîà12ÞCÒÄÃïð
GDNA
RNA

G@HC

GC

GC

GC

()*

Viral (+) RNA
1st strand (-) DNA

RNaseH?NOQPRSTIJ

HN\

LMDDNOPBLMDDNOPBPUDSOQNOPVUDSOQNOP
V WLP

Viral (+) RNA

GRT (1st strand cDNA synthesis)

GGC

YESZ[YESZ[GGC GC

XRYESZ[XRXRCXRCGC

jklmnop
cdefYESZ[qcdefYESZ[q rsêë[\$"%&éH[\()*abcdefghi%_`Yghi%
_`Y

A A
U U

YESZ[_`Y?`YA
U

GCU

U

Uracil DNA Glycosylase

GC

GC

Endonuclease

"

DNA$%
DNA
$%

HN\]^G@H

XR

YESZ[AU!
A"U UA#UDSOQNOPVUDSOQNOP
V WLP?NOQPRSTIJ

LMDDNOPBLMDDNOPBP

APOBECRT (2nd strand cDNA synthesis)

AUAUGCC

Fragmentation of viral cDNA
Hypermutated integrated provirus2©‚ƒ!ƒÅñL…©‚ƒk12êë[\X·™u78ìíJK*XòóGQKS

SIVagm1250

RT activity (cpm)

revtatgagLTRvifpolenv

vpx vprnef
LTR

hApo3G

750!-actin500"-hApo3G
250"-tubulin

mRNA Protein

SIVagmSIVagm Vif(-)

A3.01(semi-permissive)

1000

0

Mutation frequency ( x 10-2)

G:A substitution

SIVagm Vif(-)
Vif(-)
rev
tatgag

LTR

vif
pol

env

vpx vprnef
LTR

Other substitutions

554433221100

Wt

Vif(-)

WtVif(-)

Takeuchi et al, J Biol Chem.
Chem. 2005 Jan 7;280(1):375-82.

øã!¼Áææ•‚ƒéH•‚ƒ
éH[\[\•‚ƒ78òö12ÞCâ!Àô¼æÃÄÇÅæÅõ!Ò*ÝhÙè•‚ƒêë•‚ƒ
êë[\[\ð»¿

G@HIJäÁ÷ÁÂÉÁ!
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()*ùÀôÄÒ!
ÀôÄÒ!¼Áææ•‚ƒéH•‚ƒ
éH[\[\'ð»¿

1232äÁ÷ÁÂÉÁ!
ÆÂ»õÉ¼ÂÅÄÆÅÃõ

©‚ƒ!!ƒÅñ
©‚ƒƒÅñL12êë[\L12êë[\!! €ÒÄÃïð
€ÒÄÃïðúû[\úû[\„„X·™u78ìíJK*XòóGQKS
10000

40000

SIVagmSIVagm vif(-)

8000

•‚ƒêë
•‚ƒ
êë[\[\HIVHIV-1HIV-1 vif(-)

30000

6000&'()*+,-./

20000
4000

10000

0A3.010hApo3G!-actin

5

G to A substitution

5Other substitutions

4332211"-tubulin

Protein"-hApo3G
4

Human Cyclophilin AmRNA

Days after infection

Jurkat2000

SIV00Wt

Vif(-)&'()*+01./

Wt

Vif(-)

23Cyclophilin A4&'()567819

Takeuchi et al, J Virol
Virol.. 81: 8080-8090, (2007)3