Expression of CD20 after viral reactivation renders HIV-reservoir cells susceptible to Rituximab

• Published in: Nature communications Vol. 10; no. 1; pp. 3705 - 15
• Main Authors: Serra-Peinado, Carla, Grau-Expósito, Judith, Luque-Ballesteros, Laura, Astorga-Gamaza, Antonio, Navarro, Jordi, Gallego-Rodriguez, Jenny, Martin, Mario, Curran, Adrià, Burgos, Joaquin, Ribera, Esteban, Raventós, Berta, Willekens, Rein, Torrella, Ariadna, Planas, Bibiana, Badía, Rosa, Garcia, Felipe, Castellví, Josep, Genescà, Meritxell, Falcó, Vicenç, Buzon, Maria J.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 16.08.2019; Nature Publishing Group; Nature Portfolio
• Subjects: 13/1; 13/106; 13/31; 13/51; 14/19; 38/77; 631/250/254; 631/326/596/2564; 692/308/575; Anti-HIV Agents - therapeutic use; Antigens; Antigens, CD20 - metabolism; Antiretroviral agents; Antiretroviral therapy; CD20 antigen; CD4 antigen; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; Cell activation; Flow Cytometry; HIV; HIV Infections - drug therapy; HIV Infections - immunology; HIV Infections - metabolism; HIV-1; Human immunodeficiency virus; Humanities and Social Sciences; Humans; Immunologic Factors - pharmacology; Immunologic Memory; Immunotherapy; Infections; Latency; Leukocytes, Mononuclear; Lymph nodes; Lymph Nodes - cytology; Lymphocyte Activation - immunology; Lymphocytes; Lymphocytes B; Lymphocytes T; Monoclonal antibodies; multidisciplinary; Phenotypes; Rituximab; Rituximab - pharmacology; Rituximab - therapeutic use; RNA, Viral; Science; Science (multidisciplinary); Viral infections; Virus Activation; Virus Latency
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-019-11556-4

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. Here, the authors identify B lymphocyte antigen CD20 as a marker for HIV-infected T cells and provide evidence for the potential use of anti-CD20 antibodies in combination with latency reversing agents for depletion of viral reactivated CD4 T cells in patients on antiretroviral therapy.