Modulating HIV-1 envelope glycoprotein conformation to decrease the HIV-1 reservoir

被引：35

作者：

Rajashekar, Jyothi K. ^{[1
]}

Richard, Jonathan ^{[2
,3
]}

Beloor, Jagadish ^{[1
]}

Prevost, Jeremie ^{[2
,3
]}

Anand, Sai Priya ^{[2
,4
]}

Beaudoin-Bussieres, Guillaume ^{[2
,3
]}

Shan, Liang ^{[5
]}

Herndler-Brandstetter, Dietmar ^{[5
]}

Gendron-Lepage, Gabrielle ^{[2
]}

Medjahed, Halima ^{[2
]}

Bourassa, Catherine ^{[2
]}

Gaudette, Fleur ^{[2
]}

Ullah, Irfan ^{[1
]}

Symmes, Kelly ^{[1
]}

Peric, Andrew ^{[1
]}

Lindemuth, Emily ^{[6
,7
]}

Bibollet-Ruche, Frederic ^{[6
,7
]}

Park, Jun ^{[8
]}

Chen, Hung-Ching ^{[8
]}

Kaufmann, Daniel E. ^{[2
,9
]}

Hahn, Beatrice H. ^{[6
,7
]}

Sodroski, Joseph ^{[10
,11
,12
]}

Pazgier, Marzena ^{[13
]}

Flavell, Richard A. ^{[5
]}

Smith, Amos B., III ^{[8
]}

Finzi, Andres ^{[2
,3
,4
]}

Kumar, Priti ^{[1
]}

机构：

[1] Yale Univ, Sch Med, Dept Internal Med, Sect Infect Dis, New Haven, CT 06510 USA

[2] Ctr Rech CHUM, Montreal, PQ, Canada

[3] Univ Montreal, Dept Microbiol Infectiol & Immunol, Montreal, PQ, Canada

[4] McGill Univ Montreal, Dept Microbiol & Immunol, Montreal, PQ, Canada

[5] Yale Univ, Dept Immunobiol, Sch Med, New Haven, CT 06510 USA

[6] Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA

[7] Univ Penn, Dept Microbiol, Perelman Sch Med, Philadelphia, PA 19104 USA

[8] Univ Penn, Dept Chem, Sch Arts & Sci, Philadelphia, PA 19104 USA

[9] Univ Montreal, Dept Med, Montreal, PQ, Canada

[10] Harvard Med Sch, Dept Canc Immunol & Virol, Dana Farber Canc Inst, Boston, MA 02115 USA

[11] Harvard Med Sch, Dept Microbiol & Immunobiol, Div AIDS, Boston, MA 02115 USA

[12] Harvard Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA USA

[13] Uniformed Serv Univ Hlth Sci, Div Infect Dis, Bethesda, MD USA

来源：

CELL HOST & MICROBE | 2021年 / 29卷 / 06期

关键词：

BROADLY NEUTRALIZING ANTIBODIES; GP120 INNER DOMAIN; EFFECTOR FUNCTION; STRUCTURAL BASIS; INFECTED CELLS; ANTI-CLUSTER; FC-RECEPTOR; VIRAL LOAD; LATE-STAGE; EPITOPES;

D O I：

10.1016/j.chom.2021.04.014

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

Small CD4-mimetic compounds (CD4mc) sensitize HIV-1 -infected cells to antibody-dependent cellular cytotoxicity (ADCC) by facilitating antibody recognition of epitopes that are otherwise occluded on the unliganded viral envelope (Env). Combining CD4mc with two families of CD4-induced (CD4i) antibodies, which are frequently found in plasma of HIV-1-infected individuals, stabilizes Env in a conformation that is vulnerable to ADCC. We employed new-generation SRG-15 humanized mice, supporting natural killer (NK) cell and Fc-effector functions to demonstrate that brief treatment with CD4mc and CD4i-Abs significantly decreases HIV-1 replication, the virus reservoir and viral rebound after ART interruption. These effects required Fc-effector functions and NK cells, highlighting the importance of ADCC. Viral rebound was also suppressed in HIV-1+-donor cell-derived humanized mice supplemented with autologous HIV-1+-donor-derived plasma and CD4mc. These results indicate that CD4mc could have therapeutic utility in infected individuals for decreasing the size of the HIV-1 reservoir and/or achieving a functional cure.

引用

页码：904 / +

页数：19

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