NTB-A and 2B4 Natural Killer Cell Receptors Modulate the Capacity of a Cocktail of Non-Neutralizing Antibodies and a Small CD4-Mimetic to Eliminate HIV-1-Infected Cells by Antibody-Dependent Cellular Cytotoxicity

被引:1
作者
Marchitto, Lorie [1 ,2 ]
Tauzin, Alexandra [1 ,2 ]
Benlarbi, Mehdi [1 ,2 ]
Beaudoin-Bussieres, Guillaume [1 ,2 ]
Dionne, Katrina [1 ,2 ]
Belanger, Etienne [1 ,2 ]
Chatterjee, Debashree [1 ]
Bourassa, Catherine [1 ]
Medjahed, Halima [1 ]
Yang, Derek [3 ]
Chiu, Ta-Jung [3 ]
Chen, Hung-Ching [3 ]
Smith III, Amos B. [3 ]
Richard, Jonathan [1 ,2 ]
Finzi, Andres [1 ,2 ]
机构
[1] Ctr Rech CHUM, Montreal, PQ H2X 0A9, Canada
[2] Univ Montreal, Dept Microbiol Infectiol & Immunol, Montreal, PQ H2X 0A9, Canada
[3] Univ Penn, Sch Arts & Sci, Dept Chem, Philadelphia, PA 19104 USA
来源
VIRUSES-BASEL | 2024年 / 16卷 / 07期
基金
美国国家卫生研究院; 加拿大创新基金会;
关键词
NK cell activating receptors; ADCC; CD4; mimetics; nnAbs; plasma from PLWH; IMMUNODEFICIENCY-VIRUS TYPE-1; BROADLY NEUTRALIZING ANTIBODIES; CD4; DOWN-REGULATION; HIV-1; INFECTION; NK CELLS; PROTEIN; NEF; CORECEPTOR; CONFORMATION; ACTIVATION;
D O I
10.3390/v16071167
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Natural Killer (NK) cells have the potential to eliminate HIV-1-infected cells by antibody-dependent cellular cytotoxicity (ADCC). NK cell activation is tightly regulated by the engagement of its inhibitory and activating receptors. The activating receptor CD16 drives ADCC upon binding to the Fc portion of antibodies; NK cell activation is further sustained by the co-engagement of activating receptors NTB-A and 2B4. During HIV-1 infection, Nef and Vpu accessory proteins contribute to ADCC escape by downregulating the ligands of NTB-A and 2B4. HIV-1 also evades ADCC by keeping its envelope glycoproteins (Env) in a "closed" conformation which effectively masks epitopes recognized by non-neutralizing antibodies (nnAbs) which are abundant in the plasma of people living with HIV. To achieve this, the virus uses its accessory proteins Nef and Vpu to downregulate the CD4 receptor, which otherwise interacts with Env and exposes the epitopes recognized by nnAbs. Small CD4-mimetic compounds (CD4mc) have the capacity to expose these epitopes, thus sensitizing infected cells to ADCC. Given the central role of NK cell co-activating receptors NTB-A and 2B4 in Fc-effector functions, we studied their contribution to CD4mc-mediated ADCC. Despite the fact that their ligands are partially downregulated by HIV-1, we found that both co-activating receptors significantly contribute to CD4mc sensitization of HIV-1-infected cells to ADCC.
引用
收藏
页数:12
相关论文
共 65 条
  • [1] An Asymmetric Opening of HIV-1 Envelope Mediates Antibody-Dependent Cellular Cytotoxicity
    Alsahafi, Nirmin
    Bakouche, Nordine
    Kazemi, Mohsen
    Richard, Jonathan
    Ding, Shilei
    Bhattacharyya, Sudipta
    Das, Durba
    Anand, Sai Priya
    Prevost, Jeremie
    Tolbert, William D.
    Lu, Hong
    Medjahed, Halima
    Gendron-Lepage, Gabrielle
    Delgado, Gloria Gabrielle Ortega
    Kirk, Sharon
    Melillo, Bruno
    Mothes, Walther
    Sodroski, Joseph
    Smith, Amos B., III
    Kaufmann, Daniel E.
    Wu, Xueling
    Pazgier, Marzena
    Rouiller, Isabelle
    Finzi, Andres
    Munro, James B.
    [J]. CELL HOST & MICROBE, 2019, 25 (04) : 578 - +
  • [2] Impaired Downregulation of NKG2D Ligands by Nef Proteins from Elite Controllers Sensitizes HIV-1-Infected Cells to Antibody-Dependent Cellular Cytotoxicity
    Alsahafi, Nirmin
    Richard, Jonathan
    Prevost, Jeremie
    Coutu, Mathieu
    Brassard, Nathalie
    Parsons, Matthew S.
    Kaufmann, Daniel E.
    Brockman, Mark
    Finzi, Andres
    [J]. JOURNAL OF VIROLOGY, 2017, 91 (16)
  • [3] Nef Proteins from HIV-1 Elite Controllers Are Inefficient at Preventing Antibody-Dependent Cellular Cytotoxicity
    Alsahafi, Nirmin
    Ding, Shilei
    Richard, Jonathan
    Markle, Tristan
    Brassard, Nathalie
    Walker, Bruce
    Lewis, George K.
    Kaufmann, Daniel E.
    Brockman, Mark A.
    Finzi, Andres
    [J]. JOURNAL OF VIROLOGY, 2016, 90 (06) : 2993 - 3002
  • [4] HIV-1 Vpu Antagonism of Tetherin Inhibits Antibody-Dependent Cellular Cytotoxic Responses by Natural Killer Cells
    Alvarez, Raymond A.
    Hamlin, Rebecca E.
    Monroe, Anthony
    Moldt, Brian
    Hotta, Mathew T.
    Caprio, Gabriela Rodriguez
    Fierer, Daniel S.
    Simon, Viviana
    Chen, Benjamin K.
    [J]. JOURNAL OF VIROLOGY, 2014, 88 (11) : 6031 - 6046
  • [5] Two Families of Env Antibodies Efficiently Engage Fc-Gamma Receptors and Eliminate HIV-1-Infected Cells
    Anand, Sai Priya
    Prevost, Jeremie
    Baril, Sophie
    Richard, Jonathan
    Medjahed, Halima
    Chapleau, Jean-Philippe
    Tolbert, William D.
    Kirk, Sharon
    Smith, Amos B., III
    Wines, Bruce D.
    Kent, Stephen J.
    Hogarth, P. Mark
    Parsons, Matthew S.
    Pazgier, Marzena
    Finzi, Andres
    [J]. JOURNAL OF VIROLOGY, 2019, 93 (03)
  • [6] Tetherin antagonism by Vpu protects HIV-infected cells from antibody-dependent cell-mediated cytotoxicity
    Arias, Juan F.
    Heyer, Lisa N.
    von Bredow, Benjamin
    Weisgrau, Kim L.
    Moldt, Brian
    Burton, Dennis R.
    Rakasz, Eva G.
    Evans, David T.
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2014, 111 (17) : 6425 - 6430
  • [7] Elicitation of Cluster A and Co-Receptor Binding Site Antibodies Are Required to Eliminate HIV-1 Infected Cells
    Beaudoin-Bussieres, Guillaume
    Prevost, Jeremie
    Gendron-Lepage, Gabrielle
    Melillo, Bruno
    Chen, Junhua
    Smith, Amos B., III
    Pazgier, Marzena
    Finzi, Andres
    [J]. MICROORGANISMS, 2020, 8 (05)
  • [8] Biassoni Roberto, 2009, Curr Protoc Immunol, VChapter 14, DOI 10.1002/0471142735.im1410s84
  • [9] Engaging innate immunity in HIV-1 cure strategies
    Board, Nathan L.
    Moskovljevic, Milica
    Wu, Fengting
    Siliciano, Robert F.
    Siliciano, Janet D.
    [J]. NATURE REVIEWS IMMUNOLOGY, 2022, 22 (08) : 499 - 512
  • [10] Antibody and TLR7 agonist delay viral rebound in SHIV-infected monkeys (vol 563, pg 360, 2018)
    Borducchi, Erica N.
    Liu, Jinyan
    Nkolola, Joseph P.
    Cadena, Anthony M.
    Yu, Wen-Han
    Fischinger, Stephanie
    Broge, Thomas
    Abbink, Peter
    Mercado, Noe B.
    Chandrashekar, Abishek
    Jetton, David
    Peter, Lauren
    McMahan, Katherine
    Moseley, Edward T.
    Bekerman, Elena
    Hesselgesser, Joseph
    Li, Wenjun
    Lewis, Mark G.
    Alter, Galit
    Geleziunas, Romas
    Barouch, Dan H.
    [J]. NATURE, 2018, 564 (7734) : E8 - E8