TY - JOUR
T1 - Expression of CD20 after viral reactivation renders HIV-reservoir cells susceptible to Rituximab
AU - Serra-Peinado, Carla
AU - Grau-Expósito, Judith
AU - Luque-Ballesteros, Laura
AU - Astorga-Gamaza, Antonio
AU - Navarro, Jordi
AU - Gallego-Rodriguez, Jenny
AU - Martin, Mario
AU - Curran, Adrià
AU - Burgos, Joaquin
AU - Ribera, Esteban
AU - Raventós, Berta
AU - Willekens, Rein
AU - Torrella, Ariadna
AU - Planas, Bibiana
AU - Badía, Rosa
AU - Garcia, Felipe
AU - Castellví, Josep
AU - Genescà, Meritxell
AU - Falcó, Vicenç
AU - Buzon, Maria J.
PY - 2019/8/16
Y1 - 2019/8/16
N2 - © 2019, The Author(s). The identification of exclusive markers to target HIV-reservoir cells will represent a significant advance in the search for therapies to cure HIV. Here, we identify the B lymphocyte antigen CD20 as a marker for HIV-infected cells in vitro and in vivo. The CD20 molecule is dimly expressed in a subpopulation of CD4-positive (CD4+) T lymphocytes from blood, with high levels of cell activation and heterogeneous memory phenotypes. In lymph node samples from infected patients, CD20 is present in productively HIV-infected cells, and ex vivo viral infection selectively upregulates the expression of CD20 during early infection. In samples from patients on antiretroviral therapy (ART) this subpopulation is significantly enriched in HIV transcripts, and the anti-CD20 monoclonal antibody Rituximab induces cell killing, which reduces the pool of HIV-expressing cells when combined with latency reversal agents. We provide a tool for targeting this active HIV-reservoir after viral reactivation in patients while on ART.
AB - © 2019, The Author(s). The identification of exclusive markers to target HIV-reservoir cells will represent a significant advance in the search for therapies to cure HIV. Here, we identify the B lymphocyte antigen CD20 as a marker for HIV-infected cells in vitro and in vivo. The CD20 molecule is dimly expressed in a subpopulation of CD4-positive (CD4+) T lymphocytes from blood, with high levels of cell activation and heterogeneous memory phenotypes. In lymph node samples from infected patients, CD20 is present in productively HIV-infected cells, and ex vivo viral infection selectively upregulates the expression of CD20 during early infection. In samples from patients on antiretroviral therapy (ART) this subpopulation is significantly enriched in HIV transcripts, and the anti-CD20 monoclonal antibody Rituximab induces cell killing, which reduces the pool of HIV-expressing cells when combined with latency reversal agents. We provide a tool for targeting this active HIV-reservoir after viral reactivation in patients while on ART.
KW - Anti-HIV Agents/therapeutic use
KW - Antigens, CD20/metabolism
KW - CD4-Positive T-Lymphocytes/drug effects
KW - Flow Cytometry
KW - HIV Infections/drug therapy
KW - HIV-1
KW - Humans
KW - Immunologic Factors/pharmacology
KW - Immunologic Memory
KW - Leukocytes, Mononuclear
KW - Lymph Nodes/cytology
KW - Lymphocyte Activation/immunology
KW - RNA, Viral
KW - Rituximab/pharmacology
KW - Virus Activation
KW - Virus Latency
KW - ACTIVATION
KW - PERSISTENCE
KW - REPLICATION
KW - THERAPY
KW - CD4(+)
KW - SITES
KW - INFECTION
KW - LATENCY
KW - T-CELLS
KW - TISSUE
UR - http://www.mendeley.com/research/expression-cd20-after-viral-reactivation-renders-hivreservoir-cells-susceptible-rituximab
U2 - https://doi.org/10.1038/s41467-019-11556-4
DO - https://doi.org/10.1038/s41467-019-11556-4
M3 - Article
C2 - 31420544
VL - 10
SP - 3705
IS - 1
M1 - 3705
ER -
