HIV. Perspectives of Anti-HIV Research
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1 ,*+* The Japanese Society for AIDS Research The Journal of AIDS Research,- HIV Perspectives of Anti-HIV Research +, -. + / +, -. Masanori BABA, Hirotomo NAKATA, Kaori ASAMITSU, Atsushi KOMANO, + / Mika OKAMOTO and Wataru SUGIURA +, Experimental - Retrovirology Section, Medicine Branch, NCI, NIH, USA,. / +32/ HIV HIV zidovudine HIV, HIV etravirine TMC+,/ darnavir, HIV RNase H Env, Gag, Tat, Rev, Vpr, Nef, Vpu, Vif RNase H, Env HIV, HIV Gag-Gag, Tat-TAR, Rev-RRE Env-CCR /, Env-CD., Gag-Tsg +*+, Tat-Cyclin T +, (CycT + ), Rev-CRM +, Vpu-Tetherin/BST-,, Vif-APOBEC- G/F HIV. HIV : 23* 2/.. 2-/ + HIV,*+*
2 The Journal of AIDS Research Vol. +, No.,,*+* HIV 1G G- protein coupled receptor : GPCR HIV CC HIV HAART GPCR CXCR. HIV +,, HIV HIV maraviroc FDA - HIV HIV HIV HIV HIV. HIV HIV HIV-RNA DNA DNA HIV HIV RNA HIV RNase H HIV HIV CD. HIV DNA NF-kB. +* ABSABS : antibody binding site Tat HIV CD. HIV CD. HIV HIV HIV HIV HIV Tat HIV HIV NF-kB Tat NF-kB. +* ABS + HAART, /* Tat + HIV NF-kB NF-kB cluster Tat NF-kB cluster, cluster Tat HIV - cluster Tat mrna / TAR CycT+ CDK3 + HIV P-TEFb HIV 1/ +1
3 M Baba et al : Perspectives of Anti-HIV Research + + HIV cluster cluster gp+,* HIV,, Tat HIV LTR A Tat CycT+ CDK3P-TEFbHIV LTR TAR HIV B Tat CycT+ Tat CycT+ Tat TAR HIV - MazF HIV MazF HIV Tat TAR MazF HIV mrna HIV
4 The Journal of AIDS Research Vol. +, No.,,*+*., A HIV CycT+ TRM CycT+ Tat HIV-LTR, B Tat CycT+ HIV cell-based Tat CycT+ two-hybrid in silico CycT+ Tat HIV HIV HIV HIV +, sirnashrna HIV /1 HIV - +** HIV HIV HIV HIV 2 - HIV + HIV-+ sirnashrna cdna T cdna Zhou et al., Cell Host Microbe,**2 Brass et al., Science,**2 Konig et al., Cell,**2 Stremlau et al., Nature,**. Valente et al., Mol Cell,**0 Valente et al., PNAS,**3 Kawano et al, J Virol,**. Yoshida et al., Tra$ c,**2 Urano et al., FEBS Let,**2 Urano et al., Vaccine, in press 11 +3
5 M Baba et al : Perspectives of Anti-HIV Research sirnashrna mrna sirnashrna - sirnashrna HIV - HIV CD. T HIV HIV CD. T T CD. T T sirnashrna ORF CD. T sirnashrna HIV cdna ORF hnrnp U N ORF Brd C +,, +-. cdna sirnashrna HSV-+ STING ORF 3+*, HIV cdna cdna HIV CXCR. ++ cdna cdna complexity, cdna CD. cdna cdna HIV T +-, +. CD. HIV cdna cdna cdna HIV 12,*
6 The Journal of AIDS Research Vol. +, No.,,*+* DNA J B 0 /HSP.* B 0, bromodomain contain- MazF ing. brd. C SEC+. -like + a SEC+. L+ a C HIV HIV in vitro PBMCs, CD. sirnashrna cdna T MazF HIV X. R/ R/ X. cdna HIV T MazF cdna HIV HIV HIV HIV mrna HIV ACA HIV cdna HIV CD. T MazF CD. T 0* MazF CD. T RNA MazF HIV CD. T MazF HIV HAART HIV HIV Tat RNA MazF HIV HAART MazF HIV mrna ACA / RNA HIV HAART +/, +0 HIV ATP MazF HIV mrna rrna trna DNA ACA DNA RNA prevention eradication HIV ACA,.* HIV robustness TAR MazF HIV Tat TAR MazF HIV mrna HIV eradication. eradi- 13,+
7 M Baba et al : Perspectives of Anti-HIV Research cation Miraglia LJ, Bushman FD, Young JA, Chanda SK : Global analysis of host-pathogen interactions that regu- late early-stage HIV-+ replication. Cell +-/ :.30*,,**2. 2 Go# SP : Knockdown screens to knockout HIV- +. Cell + Alkhatib G, Combadiere C, Broder CC, Feng Y, Kennedy +-/ :.+1.,*,,**2. PE, Murphy PM, Berger EA : CC CKR / : a RANTES, 3 Ishikawa H, Barber GN : STING is an endoplasmic re- MIP-+ alpha, MIP-+ beta receptor as a fusion cofactor for ticulum adaptor that facilitates innate immune signalling. macrophage-tropic HIV- +. Science,1, : +3// +3/2, Nature.// : ,,**2., Dean M, Carrington M, Winkler C, Huttley GA, Smith MW, Allikmets R, Goedert JJ, Buchbinder SP, Vittingho# +* Ishikawa H, Ma Z, Barber GN : STING regulates intracellular DNA-mediated, type I interferon-dependent E, Gomperts E, Donfield S, Vlahov D, Kaslow R, Saah innate immunity. Nature.0+ : 12213,,,**3. A, Rinaldo C, Detels R, O Brien SJ : Genetic restriction of HIV-+ infection and progression to AIDS by a de- ++ Feng Y, Broder CC, Kennedy PE, Berger EA : HIV-+ entry cofactor : functional cdna cloning of a sevenletion allele of the CKR/ structural gene. Hemophilia transmembrane, G protein-coupled receptor. Science,1, : Growth and Development Study, Multicenter AIDS 21, 211, Cohort Study, Multicenter Hemophilia Cohort Study, +, Valente ST, Go# SP : Inhibition of HIV-+ gene expres- San Francisco City Cohort, ALIVE Study. Science,1- : sion by a fragment of hnrnp U. Mol Cell,- : /310*/, +2/0 +20,, +330.,**0. - Gulick RM, Lalezari J, Goodrich J, Clumeck N, DeJesus +- Urano E, Kariya Y, Futahashi Y, Ichikawa R, Hamatake E, Horban A, Nadler J, Clotet B, Karlsson A, Wohlfeiler M, Fukazawa H, Morikawa Y, Yoshida T, Koyanagi Y, M, Montana JB, McHale M, Sullivan J, Ridgway C, Yamamoto N, Komano J : Identification of the P-TEFb Felstead S, Dunne MW, van der Ryst E, Mayer H : complex-interacting domain of Brd. as an inhibitor of Maraviroc for previously treated patients with R/ HIV- HIV-+ replication by functional cdna library screening + infection. N Engl J Med -/3 : +.,3 +..+,,**2. in MT-. cells. FEBS Lett /2, :.*/-.*/2,,**2.. Karn J : Tackling Tat. J Mol Biol,3- :,-/,/., Urano E, Ichikawa R, Morikawa Y, Yoshida T, Koyanagi / Brass AL, Dykxhoorn DM, Benita Y, Yan N, Engelman A, Xavier RJ, Lieberman J, Elledge SJ : Identification of T, Komano J : T cell-based functional cdna library screening identified SEC+. -like + a carboxy-terminal dohost proteins required for HIV infection through a func- main as a negative regulator of human immunodeficiency tional genomic screen. Science -+3 : 3,+ 3,0,,**2. virus replication. Vaccine, in press. 0 Zhou H, Xu M, Huang Q, Gates AT, Zhang XD, Castle +/ Zhang Y, Zhang J, Hoeflich KP, Ikura M, Qinq G, Inouye JC, Stec E, Ferrer M, Strulovici B, Hazuda DJ, Espeseth M : MazF cleavages cellular mrnas specifically at ACA AS : Genome-scale RNAi screen for host factors required to block protein synthesis in Escherichia coli. Mol Cell for HIV replication. Cell Host Microbe. :.3/ /*.,,**2. +, : 3+-3,-,,**-. 1 Konig R, Zhou Y, Elleder D, Diamond TL, Bonamy +0 Zhang Y, Zhang J, Hara H, Kato I, Inouye M : Insights GM, Irelan JT, Chiang CY, Tu BP, De Jesus PD, Lilley into the mrna cleavage mechanism by MazF, an mrna CE, Seidel S, Opaluch AM, Caldwell JS, Weitzman MD, interferase. J Biol Chem,2* : -+.* -+/*,,**/. Kuhen KL, Bandyopadhyay S, Ideker T, Orth AP, 2*,,
Gag. Gag-Gag. TSG101 Nedd4. Two-Hybrid HIV Gag. Two-Hybrid. Two-Hybrid
CytoTrap HIV Gag AnnexinA2 AUP1 AUP1 HIV AUP1 N Gag CytoTrap Gag-Gag TSG101 Nedd4 Two-Hybrid Two-Hybrid HIVGag Gag Two-Hybrid HIV Gag Gag HIV Two-Hybrid CytoTrap cdna Gag Gag CytoTrap Gag CytoTrap Gag-Gag
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Received 26 August 2008; revised 10 October 2008; accepted 21 October Available online 7 November Edited by Ivan Sadowski
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