HIV Anti-HIV Neutralizing Antibodies

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,**/ The Japanese Society for AIDS Research The Journal of AIDS Research : HIV HIV Anti-HIV Neutralizing Antibodies * Junji SHIBATA and Shuzo MATSUSHITA * Division of Clinical Retrovirology and Infectious Diseases, Center for AIDS Research, Kumamoto University human immunodeficiency virus : HIV gp+,* SU gp.+ TM ENV HIV gp+,* gp.+ HIV, Env gp.+ +, HIV Antibody-dependent cell-mediated cytotoxicity : ADCC HIV -,. HIV HIV gp+,* variable region V+ V/ loop conserved region C+ C/ gp.+ / gp+,* : 20* *2++,, +,**/ 2 -* CD. CCR/ CXCR. gp.+ HIV + + CD. CD. binding domain ; CD.bd CD. CD. induced ; CD.i V, V- gp+,* gp.+ HIV + CD.bd gp+,* CD. HIV HIV CD.bd Tcell tropic primary isolate CD.bd HIV IgG+b+, HIV gp+,* primary isolate CD.bd in vivo 0 Haynes IgGb+, HIV gp.+,f/.e+* 1 IgGb+, +0+ 1

J Shibata and S Matsushita : Anti-HIV Neutralizing Antibodies + HIV-+ gp+,* CD.-bindig domain IgGb+,, //3/0.D, +/e IgGb+, gp+,* CD.-induced epitope +1b,.2D Fab gp+,* a+, mannose,g+, gp+,* V, loop 031D gp+,* V- loop..1-/,d,,+2,, *./b gp.+ transmembrane,f/,.e+*, Z+- Cardiolipin + HIV CD.bd gp+,* T 2 gp+,* CD.bd, CD.i HIV CD.i 3 gp+,* CD. CD.i soluble CD. CD.i +1b gp+,* V+ V, stem b-strand C. primary isolate Fab fragment +* CD.i HIV CD. HIV Fab whole IgG - V, V, V, V, V+ V, V+ V, ++ V- +, +0, 2

The Journal of AIDS Research Vol. 1 No. -,**/. V- V, V- V- HIV V-..1-/,D V- tip B /* V- V- V- V, -* -/ tip type II turn V- HIV NMR V- +- X. V- CXCR. SDF-+ +. HIV V- HIV V- V- HIV / gp+,* gp+,*,g+, primary isolate 0 gp.+ gp+,* CD. gp.+ HIV gp.+,f/.e+* g.+ Cardiolipin polyspecific autoantibody 1 CDR- HIV Simian immunodeficiency virus : SIV B +/. escape mutant in vivo +0 +1 HIV escape mutant escape mutant +0 long term non-progressor : LTNP +2 LTNP HIV HIV +0-3

J Shibata and S Matsushita : Anti-HIV Neutralizing Antibodies Env HIV /* HIV Env HIV +0 ENV Wei +0 Wang C- HIV +3 HIV LTNP +2 SIV,*,,+ HIV HIV gp+,* HIV,, HIV gp+,* gp.+,- Env gp+,* V, loop Env,. gp+,* V- rabbit HIV,/ HIV HIV CD. HIV HIV CD.,0 + Zwick MB et al :Broadly neutralizing antibodies targeted to the membrane-proximal external region of human immunodeficiency virus type + glycoprotein gp.+. J Virol 1/, +*23, +*3*/,,**+., Dimmock NJ : Neutralization of animal viruses. Curr Top Microbiol Immunol +2- : + +.3, +33-. - Tyler DS et al :Identification of sites within gp.+ that serve as targets for antibody-dependent cellular cytotoxicity by using human monoclonal antibodies. J Immunol +./ : -,10 -,2,, +33*.. Koup RA et al :Antibody-dependent cell-mediated cytotoxicity directed by a human monoclonal antibody reactive with gp+,* of HIV-+. AIDS / : +-*3 +-+., +33+. / Kwong PD et al :Oligomeric modeling and electrostatic analysis of the gp+,* envelope glycoprotein of human immunodeficiency virus. J Virol 1. : +30+ +31,,,***. 0 Kessler JA et al :Recombinant human monoclonal antibody IgGb+, neutralizes diverse human immunodeficiency virus type + primary isolates. AIDS Res Hum Retroviruses +- : /1/ /2,, +331. +0. +*

The Journal of AIDS Research Vol. 1 No. -,**/ 1 Haynes BF et al :Cardiolipoin polyspecific autoreactivity in two broadly neutralizing HIV-+ antibodies. Science -*2 : +3*0 +3*2,,**/. 2 Hioe CE et al :Inhibition of human immunodeficiency virus type + gp+,* presentation to CD. Tcells by antibodies specific for the CD. binding domain of gp+,*. J Virol 1/ : +*3/* +*3/1,,**+. 3 Decker JM et al :Antigenic conservation and immunogenicity of the HIV coreceptor binding site. J Exp Med,*+ : +.*1 +.+3,,**/. +* Labrijn AF et al :Access of antibody molecules to the conserved coreceptor binding site on glycoprotein gp+,* is sterically restricted on primary human immunodeficiency virus type +. JVirol 11 : +*//1 +*/0/,,**-. ++ Cao J et al :Replication and neutralization of human immunodeficiency virus type + lacking the V+ and V, variable loops of the gp+,* envelope glycoprotein. J Virol 1+ : 32*2 32+,, +331. +, Pinter A et al :TheV+/V, domain of gp+,* is a global regulator of the sensitivity of primary human immunodeficiency virus type + isolates to neutralization by antibodies commonly induced upon infection. J Virol 12 : /,*/ /,+/,,**.. +- Sharon M et al :Alternative conformations of HIV-+ V- loops mimic b hairpin in chemokines, suggestion a mechanism for coreceptor selectivity. Structure ++ :,,/,-0,,**-. +. Yonezawa A et al :Replacement of the V- region of gp +,* with SDF-+ preserves the infectivity of T-cell line tropic human immunodeficiency virus type +. J Virol 1/ :.,/2.,10,,**+. +/ Schmitz JE et al :E#ect of humoral immune responses on controlling viremia during primary infection of rhesus monkeys with simian immunodeficiency virus. J Virol 11 :,+0/,+1-,,**-. +0 Wei X et al :Antibody neutralization and escape by HIV-+. Nature.,, : -*1 -+,,,**-. +1 Scarlatti G et al :Interplay of HIV-+ phenotype and neutralizing antibody response in pathogenesis of AIDS. Immunol Lett /+ :,-,2, +330. +2 Pilgrim AK et al :Neutralizing antibody responses to human immunodeficiency virus type + in primary infection and long-term-nonprogressive infection. J Infec Dis +10 : 3,. 3-,, +331. +3 Wang FX et al :Emergence of autologous neutralization-resistant variants from preexisting human immunodeficiency virus (HIV) quasi species during virus rebound in HIV type +-infected patients undergoing highly active antiretroviral therapy. J Infec Dis +2/ : 0*2 0+1,,**,.,* Shibata R et al :Neutralizing antibody directed against the HIV-+ envelope glycoprotein can completely block HIV-+/SIV chimeric virus infections of macaque monkeys. Nat Med / :,*.,+*, +333.,+ Emini EA et al :Prevention of HIV-+ infection in chimpanzees by gp+,* V- domain-specific monoclonal antibody. Nature -// : 1,2 1-*, +33,.,, Zwick MB et al :Neutralization synergy of human immunodeficiency virus type + primary isolates by cocktails of broadly neutralizing antibodies. J Virol 1/ : +,+32 +,,*2,,**+.,- Li H et al :Recombinant multi-envelope vaccine induce predefined epitope-specific antibodies against HIV-+. Immunol Lett 2. : +/- +/1,,**,.,. Barnett SW et al :The ability of an oligomeric human immunodeficiency virus type + (HIV-+) envelope antigen to elicit neutralizing antibodies against primary HIV-+ isolates is improved following partial deletion of the second hypervariable region. J Virol 1/ : //,0 //.*,,**+.,/ Keller PM et al :Identification of HIV vaccine candidate peptides by screening randam phage epitope libraries. Virology +3- : 1*3 1+0, +33-.,0 Douek D et al :HIV preferentially infects HIV-specific CD. Tcells. Nature.+1 : 3/ 32,,**,. +0/ ++