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+3 腚腯腱腌腊腐腝腘腎腗腕腏腋腖腠腵 +3 腚腯腱腌腊腐腝腘腎腗腕腏腋腖腠腵 HIV-+ HTLV-I : 腔腗腑腁腉腔腒腓腍腊腓腇 腸腃腺膋腵膀腃 : 膖膃膸腶腵膗膃臙臇臂膹 膵膃膸膜膸膸臙臇臕膣膜膵腷腵膄膸膲2 : 122/,**0 膘膭腤腍腒腯膘膊膙腶腵膗膃臙臇腦腏腳臙臇腤腐腣 臭臘腲腣腗腛腏膎膊腤腍腒腯膘膊膙腶腵膗膃腥臹腦腊膿膨膹腠腉腝腛膎膊膘膊膙腶腵膗膃臙臇腥臑膾+32* T 膴腦膖膚膍腤臚腖腰腛膎膊 T 膴膠腵膗膃 I human T-cell leukemia virus type I : HTLV-I腉腯腚腥臚腤膠腐腐腾膚膏膕膚膁膃腼腠臡膒腦膺膨腳腛臤臐 腷腵膄臰腖腰腛腥腦臼腥膦腲腠腉腝 腛腥腎腫腗腰腣腊HTLV-臙臇腠膎膊膘膊膙腶腵膗膃腤 腑腥膈腉臓臜腲腘腯腬腋腤腣腝腛臙臇臎腘腏腷腵膄腥臝膟腶腵膗膃腠腉腯膎膊膨腳腶腵膗膃 HIV腊腞腪膙膐腡腚腥腦腋腭腎腤腗腟 腊腝腛腚腥膭腦臌腪腟臃膿腤腢膇腇臌膿腧腡 腮腣臱腠腦腼膚膊膙腃膗膫膶腦腊膻腡臟腱腰腯 腨腠腤腣腝腟腊腯腔腰腨腠 HTLV-HIV 腥臙臇腦腑腥至腲腌臯腊臲腝腟腊腯膁膚膑膂腶膓腠腦 HTLV-HIV 膷腗腚腥臙臇腥臅膭腲臗腘腯腔腡 膼膑腡腗腛膁膚膑膂腶膓腦腔腰腎腭腥膎膊膘膊膙 腶腵膗膃臙臇腥腲臫腌腯腠腫膥腣至腲腌腛 腡臫腌腟腊腯腦腟腅 CCR/ 腩腜腢 aplaviroc 腅腣腳腞腤腙腲腃腡腪 腝腭腙腨 腱膔 膊膔 腗膲 膗臒 臂膹 膵膃膸膜膸膸臙臇臕膣膧膛膬膼腰膺腢臌膫 +腆腂腈腄 +33* 膞膂膊臃腤膕腞腗腛 HAART 臌膳 膯臆臌膳腡腗腛 AIDS 腘腯膩膸臌膳腦膶腎腤腐腣膭腲 臈腓腟腐腛腗腎腗膁腦膰膛膺腥臞腣腢腒腟腰腣腊膮腏臻腗腟 腊腯膁腦 HIV-+ 腘腯腇臌膳腥膶腦臶腫膽膄腥膝腞腡腣腝腟腍腮膁腦膰膛膺腤腫臊腗腎腫膁腦膺腏膡腨腗腣腊 膡腨腗腤腑腊臄腥臸腥膴腚膤腥膮腡腣腝腟腊腯腦腔腰 腨腠膁腦 HIV-+ 腤腫臥腣臨 HIV 腥膝膽腡 腗腟臷膴腹腠腉腯腻膔腹腵膚膘膅膐膇腃 CCR/腘腯膝臐腥腴膚膇腽膌膃膊腥臙臇腲腪腟腐腛腏臶臍腗腛 spirodiketopiperazine 臃膚腾腥膝膞aplaviroc AVC膁腦膺腲臀腩 R/-HIV-+ 腥膼腷腟臜膾臈腥膘膭膔膉膗臒 NOG-SCID 膒腶膃腠腫臊腣臨腶腵膗膃膹腠腻膔腹腵膚 RANTESCCR/ 腧腥臔臯腤腦腱腙腎腗腎膢臋腲腌腙RANTES CCR/ 腲膱腗腛腨臊膑膫膮膑腤腗腎膵腗腣腊 腔腡腣腢腲腭腎腤腗腟腐腛臬膦腠腦腚腥腬腋腣臔膭 臰腗膪腌腟腕腑臶臍腥 AVC CCR/ 腡腥臠臺腥臩臔膭腤腞腊腟腫腰腯,腦腟腅 CCR/ 腩腜腢 aplaviroc 腅腮腬腃腴腥腛腰 ,**+ CCR/ 腘腯膝臐 spirodiketopiperazine 臃膚腾膙膐 Maeda & Mitsuya, J Biol Chem ,10 : -/+3.-/,**, ,**+腊腠 ,**. 腤腦腚腥 + 腞腠腉腯 aplavirocAK 0*, AVC腅腄+臜膾腠臊腣膹IC/* : *., nM腅腁 腥臨 HIV-+ 膓腍腴腵膵臸 RTIs腅腁 膐膙膈腴腃膆膵臸 PIs腅腇 腑臣臵膁腦腪腙 Maeda & Mitsuya, J Virol 12 : 20/., ,**.腅腁 膘膭膔膉 huPBL-NOG-SCID 膒腶膃腥臒腠腫臊腣臨 HIV 腘腔腡 Nakata & Mitsuya, J Virol 13 : ,*21, ,**/膋腎臐臉腮 : 膧膰腄腈0*02/*1 膖腁致臉臎臢膡/- 膖膃膸腶腵膗膃臙臇腖膪腺腷腵膄臙臇腂腭Fax : *1/1/+.*.3 ,**0 0 / 膜腓膩 + Aplaviroc 腥臩,**0 The Japanese Society for AIDS Research The Journal of AIDS Research +, 12
8

HIV- HTLV-I : ˘ˇ˘ˆ · - Aplaviroc CCR/ ,**0 AVC -H ˘ˇCCR/ˆ˙˝˛ ˚CCR/ ˜ ! " #$ %&’ CCR/ CCR/ ˆ˙˝ ()*+,-,./ 0)1 2 34$56 ’ " 7 #8 9 :Maeda & Mitsuya, J Biol Chem ,2+

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Page 1: HIV- HTLV-I : ˘ˇ˘ˆ · - Aplaviroc CCR/ ,**0 AVC -H ˘ˇCCR/ˆ˙˝˛ ˚CCR/ ˜ ! " #$ %&’ CCR/ CCR/ ˆ˙˝ ()*+,-,./ 0)1 2 34$56 ’ " 7 #8 9 :Maeda & Mitsuya, J Biol Chem ,2+

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. CCR/*¥+,m{H�[*�|H�+K}¦+'0gX'�*�YK�+Z&,5 §¨2#>.QR'`[*#I+� ©iZªM��. AVCX CCR/X.~«�[.¬��H­�`[�U0ZL�<�5

,+ ��� CCR/�� aplaviroc�01�2345�W# ,**+�� CCR/�]P��H spirodiketopiperazine

stu*01 Maeda & Mitsuya, J Biol Chem ,10 : -/+3.�-/,**, ,**+�� 202 ,**.��#>. +U23� aplaviroc�AK0*, AVC� � +� $xO��2�l'��*A+IC/* : *., nM�� ®�.�HIV-+y ¯°��±�}¦yRTIs�� �"²��³}¦y PIs�´ X!Mµ¶a�*�V¢ Maeda & Mitsuya, J Virol 12 : 20/., ,**.�� ���� huPBL-NOG-SCID ��� .�2L�l'�HIV��*APgX Nakata & Mitsuya, J Virol 13 : ,*21, ,**/�

�+��; : ���� ·0*0�2/*1 ��¸¹�º»�S�/- ����� ��������������Fax : *1/�1/+�.*.3

,**0� 0¼ / �� 6 + Aplaviroc.¬�

�,**0 The Japanese Society for AIDS Research The Journal of AIDS Research

+, �12

Page 2: HIV- HTLV-I : ˘ˇ˘ˆ · - Aplaviroc CCR/ ,**0 AVC -H ˘ˇCCR/ˆ˙˝˛ ˚CCR/ ˜ ! " #$ %&’ CCR/ CCR/ ˆ˙˝ ()*+,-,./ 0)1 2 34$56 ’ " 7 #8 9 :Maeda & Mitsuya, J Biol Chem ,2+

������ ����� AVC����������azidothymidine, nevirapine�� ��������� �in-

dinavir�� !��� �AMD-+**� "#$ CD.�� %&��� �T-,*� �'()*+,-./012�34567(�8�� �Nakata & Mitsuya� 9:;<=�� ��� AVC>

CCR/?56-@�A&BC$ �KDD : E- nM� �F���G� HIJKL �RANTES� ) CCR/M)A&>NOP�PQR�STO� RANTES� CCR/�U� V�G5WXYZ+[. V\]>����.7(�8�� �Maeda & Mitsuya, J Virol 12 : 20/., ,**.��

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Page 3: HIV- HTLV-I : ˘ˇ˘ˆ · - Aplaviroc CCR/ ,**0 AVC -H ˘ˇCCR/ˆ˙˝˛ ˚CCR/ ˜ ! " #$ %&’ CCR/ CCR/ ˆ˙˝ ()*+,-,./ 0)1 2 34$56 ’ " 7 #8 9 :Maeda & Mitsuya, J Biol Chem ,2+

-� Aplaviroc� CCR/��������� ��� ,**0������ �� AVC ������������������������- H��� CCR/

����� CCR/� �!��"�����#$ ��%&'� CCR/�CCR/��� ()*+,-,./0)1 2��34$56�����'��"�7 ���#8��9�� :Maeda & Mitsuya, J Biol Chem ,2+ :

+,022�+,032, ,**0;< =>��?@ /,-A� AVCBCCR/ :C ,; �DEFG)���H�EFG)AIJKL�MNOPQRS�#$��TU :V�W;�= #$�X�� ������ CCR/��� :SCH-C, TAK-

113; �YTTZ=[���Y "\]^ �_A= #$�`B����"� :C -; :Yin, Das, & Mitsuya, Cell

Mol Life Sci, ,**0, in press;< a����� b��c CCR/

��� 7 �#$�`�� :ERd)1./0)1eJ;�f� :Maeda & Mitsuya, J Biol Chem ,2+ : +,022�+,032,

,**0;� �gZU7 �./����h�� spirodike-

topiperidine������()P,i)S����@j CCR/��� /kG)�$J�h��"�<

.� Aplaviroc�HIV-+���������� ���a�� AVCB RANTES�l Q.mG)�

CCR/� noe�������^pqRr��"s����� AVC�tu CCR/��� #$�v�� CCR/ PQRSBQ.mG)e�TZwHIVxy� z�{|�]"�}~�����A 7 ��!Y����s��PQRS [� :" .�/�H�EFG)�#; �HIV-+xy�v�A�U�B�Q.mG)e������l{|��"�_B��s��$�^��� :C - ; Gly+0-, Ile+32

�l;<s>��/,-�� HIV-+xy 4�v�����-,�RS���%���$��/kG)��s�AQ.mG)���-, ���e������"�HIV-+� ./0)1B� A��s������5L� :Maeda

& Mitsuya, J Biol Chem ,2+ : +,022�+,032, ,**0;<Q.mG)���-,����b& �HIV����

U�' : �; ���(������A����� )��*UQ.mG)e������s��Z��'� {|�+,A��"< %�� CCR/�tuQ.mG)���-,B��xy��-��.��/���0� 1��¡ ��"��">�9B��< ¢£ ¤¥J8��� e�¦§ 7 ��������ZU.�'�tu�'� {| ¨�"@j�� ©ª�/kG) � O�«\�¬����5L�<

/� Aplaviroc�HIV-+�������������AVC�2­A 3®¯& :" -n¯&; A AIDS°±�

4�TZw5�A6 KL�� «7��HIV²O�³��s�B�KL�B� 89 ´µ�B[� °±A¶�L�3®¯&� @�"°± enrollment�:;� �g��B�!��<c =·' :congeners; :^� back-

up spirodiketopiperadine >?'�¸,:A��<

0� ��s ¤¥^���� AVCB CCR/ �DEFG)�

��H�EFG)AIJKL�MNOPQRS�#$��= #$�`�� ������ CCR/��� :SCH-C,

TAK-113; �"\]^ @A����"�s��¶¹��<º� CCR/ AVC#$PQRS [� :" .�/�H�EFG)�#; �HIV-+xy�v�A�U�B�� Q.mG)e������l{|��"�_B��s��$�^��� HIV-+xy 4�v�����-,�RS���%���$��/kG)��s�A� Q.mG)���-, ���e������"�HIV-+� ./0)1B� A��s�����< sL� /,-�.�'�tu�'� {| ¨�"�HIV-+e������@�"»A� B,� ¼� CD���Y ��KL�<

+ ; Maeda K, Yoshimura K, Shibayama K, Habashita H,

Tada H, Sagawa K, Miyakawa T, Aoki M, Fukushima

D, Mitsuya H : Novel low molecular weight spirodiketo-

piperazine derivatives potently inhibit R/ HIV-+ infec-

tion through their antagonistic e#ects on CCR/. J Biol

Chem ,10 : -/+3.�-/,**, ,**+.

, ; Nakata H, Maeda K, Miyakawa T, Shibayama S, Matsuo

M, Takaoka Y, Ito M, Koyanagi Y, Mitsuya H : Potent

anti-R/ human immunodeficiency virus type + e#ects of a

CCR/ antagonist, AK0*,/ONO.+,2/GW21-+.*, in a

novel human peripheral blood mononuclear cell non-

obese diabetic-SCID, interleukin-, receptor g-chain-

knocked-out AIDS mouse model. J Virol 13 : ,*21�,*30,

,**/.

- ; Maeda K, Das D, Ogata-Aoki H, Nakata H, Miyakawa

T, Tojo Y, Norman R, Takaoka Y, Ding J, Arnold E,

Mitsuya H : Structural and molecular interactions of

CCR/ inhibitors with CCR/. J Biol Chem ,2+ : +,022�+,032, ,**0.

. ; Yin PD, Das D, Mitsuya H : Overcoming HIV drug

resistance through rational drug design based on molecu-

lar, biochemical, and structural profiles of HIV resist-

ance. Cell Mol Life Sci, ,**0 (In press)

M Matsuoka et al : HIV-+ and HTLV-� : From Bench to Bedside

: +. ;2*

Page 4: HIV- HTLV-I : ˘ˇ˘ˆ · - Aplaviroc CCR/ ,**0 AVC -H ˘ˇCCR/ˆ˙˝˛ ˚CCR/ ˜ ! " #$ %&’ CCR/ CCR/ ˆ˙˝ ()*+,-,./ 0)1 2 34$56 ’ " 7 #8 9 :Maeda & Mitsuya, J Biol Chem ,2+

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��) Pol"#$ CTL ! NL.-,�� CD.T%&,{D5! �=%&'(�)\�DR? xy! �� .Ec�� !NL.-,�� CD.T%&,{D5 ! %&'(�)\�`<>4R? �� ! �,�HLA-B*-/*+��) CTL<�\deR1! �=HIV-+89:�}\�|�� ! zPQ<>4R?SQP�vw>P! Nef,-.HLAEF� I�downregulation,-45! �K�HIV-+"#$ CTL @�/01IJ|.1! x�,HIV-+"#$ CTL�%&'(�)CHIV-+89:�,��\��<=�=%&'(�)\��HIV-+"#$ CTL1��|.SC1 P>,<4R?xy! HIV-+��¡x��¢$�£.¤Ecq¥�¦,{|.HIV-+"#$ CTL�/0\deR? §C¨��HIV-+"#$ CTLEc�� ! NL-M,*A,{D5 �=:�}\�DR? xy! CD.T%&C©45¤Ecq¥�¦%&,{D5 ! NL-.-,,{D5�§C¨��CTLEc����=HIV-+89:�}1zPQR? @S�! NL.-,�� CD.T%&CNL.-,��¤Ecq¥�¦�HIV-+"#$ CD2T%&�89ª«}\deRCS�!

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The Journal of AIDS Research Vol. 2 No. , ,**0

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The Journal of AIDS Research Vol. 2 No. , ,**0

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