Cell-to-Cell Transmission of HIV-1 Is Required to Trigger Pyroptotic Death of Lymphoid-Tissue-Derived CD4 T Cells
Year: 2015
Type: article
Abstract: The progressive depletion of CD4 T cells underlies clinical progression to AIDS in untreated HIV-infected subjects. Most dying CD4 T cells correspond to resting nonpermissive cells residing in lymphoid tissues. Death is due to an innate immune response against the incomplete cytosolic viral DNA intermediates accumulating in these cells. The viral DNA is detected by the IFI16 sensor, leading to inflammasome assembly, caspase-1 activation, and the induction of pyroptosis, a highly inflammatory form of programmed cell death. We now show that cell-to-cell transmission of HIV is obligatorily required for activation of this death pathway. Cell-free HIV-1 virions, even when added in large quantities, fail to activate pyroptosis. These findings underscore the infected CD4 T cells as the major killing units promoting progression to AIDS and highlight a previously unappreciated role for the virological synapse in HIV pathogenesis.
Source: Cell Reports
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,620
Funders: A.P. Giannini Foundation, National Institutes of Health, University of California, San Francisco, National Institute on Drug Abuse, National Institute of Allergy and Infectious Diseases, National Center for Chronic Disease Prevention and Health Promotion, National Institute on Minority Health and Health Disparities
Awards: The contribution of unintegrated HIV-1 to latency and to models of latency, HIV-Induced CD4 T-Cell Depletion: An Innate Host Defense Gone Awry?, G3181090803, HIV-1 Replication Without Integration, HIV without AIDS: A Radically Different Approach to Help the Developing World, G6324639374, Martin Delaney Collaboratory to Eradicate HIV-1 Infection, G9000147187, Integrative Microbiology Program, UCSF-Bay Area Center for AIDS Research, G956777828
OpenAlex ID: W1871039033