Efficient HIV-1 Trans Infection of CD4+ T Cells Occurs in the Presence of Antiretroviral Therapy. (24th May 2019)

• Record Type: Journal Article
• Authors: Rappocciolo, Giovanna; Sluis-Cremer, Nicolas; Rinaldo, Charles R
• Is Part Of: Open forum infectious diseases. Volume 6:Number 7(2019)
• Publication Date: 2019-05-24
• Subjects: antigen-presenting cells -- ART -- B lymphocytes -- dendritic cells -- HIV -- trans infection; Communicable diseases -- Periodicals; Medical microbiology -- Periodicals; Infection -- Periodicals; 616.9
• DOI: 10.1093/ofid/ofz253
• Languages: English
• ISSNs: 2328-8957

Abstract

Abstract: Background: Antiretroviral therapy (ART) has dramatically improved the quality of life of people with HIV-1 infection (PWH). However, it is not curative, and interruption of ART results in rapid viral rebound. Cell-to-cell transfer of HIV-1, or trans infection, is a highly efficient mechanism of virus infection of CD4 + T cells by professional antigen-presenting cells (APCs), that is, dendritic cells (DCs), macrophages, and B lymphocytes. Methods: APC from HIV seronegative donors treated with ART in vitro (CCR5 agonist, NRTI, PI and NNRTI, alone or in combination), were loaded with HIV R5-tropic HIVBal and mixed with autologous or heterologous CD4 + T lymphocytes to assess trans infection. Ex vivo APC from chronic HIV-infected MACS participants before and after initiation of ART, were also loaded with HIV R5-tropic HIVBal and tested for trans infection against autologous or heterologous CD4 + T lymphocytes. Virus replication was measured by p24 ELISA. Results: Here we show in vitro that antiretroviral drugs did not block the ability of DCs and B cells to trans -infect CD4 + T cells, although they were effective in blocking direct cis infection of CD4 + T cells. Moreover, ex vivo DCs and B cells from ART-suppressed PWH mediated efficient HIV-1 trans infection of CD4 + T cells, which were resistant to direct cis infection. Conclusions: Our study supports a role for HIV-1 trans infection in maintenance of the HIV-1 reservoir during ART.