Our work
The Mamede Lab studies how HIV-1 interfaces with innate immunity, with a particular focus on early replication events and their consequences for infection, immune activation, and neuropathogenesis. We integrate molecular virology with quantitative live and super-resolution imaging, machine-learning–based image analysis, and single-cell and spatial transcriptomics to resolve HIV–host interactions across scales, from individual viral particles to complex human tissue models.
Our work has defined key early steps of HIV-1 replication, including the timing and cellular location of capsid disassembly and its direct link to productive infection. We also uncovered a two-step innate immune sensing mechanism in which host factors recognize the incoming viral capsid and enable cGAS activation during early post-entry replication, establishing the viral core as a critical trigger of innate immune surveillance. These discoveries have provided a framework for understanding how innate sensors detect HIV despite its strategies to shield viral nucleic acids.
A major focus of the lab is HIV infection of the central nervous system, where chronic innate immune activation contributes to neuroinflammation and neuronal dysfunction even in the era of effective antiretroviral therapy. To address this, we developed microglia-containing cerebral organoids that support productive HIV infection and recapitulate microglia-driven inflammatory responses in a human brain-like environment. Using these models, we investigate how cGAS-dependent innate immune pathways in microglia shape neuroinflammatory signaling, neuronal stress, and therapeutic responsiveness, including interactions with comorbid factors such as substance exposure.
In parallel, we are examining how interferon-regulated host pathways influence HIV replication and immune outcomes, including how viruses may differentially exploit or evade innate immune signaling components under inflammatory conditions. Complementing these efforts, the lab is building an HIV-1 epitranscriptomics program using nanopore direct RNA sequencing to define viral RNA modification landscapes and determine how epitranscriptomic regulation impacts viral gene expression, innate immune sensing, and persistence.
Together, our research aims to define fundamental principles of HIV–innate immune interactions in both immune and neural contexts, with the long-term goal of identifying host-directed strategies to limit viral replication, neuroinflammation, and HIV-associated neurological disease.
Impact of work
Technology
Funding
Current Funding
Principal Investigator:
- R01MH139377: Role Of Innate Immunity to NeuroHIV in the cART Era
- R61/R33DA058348: Molecular Pathways of Innate Immunity and Substance Abuse in NeuroHIV
Co-Investigator:
- (R61/R33)AI169661: Coupling Epitranscriptomics to Molecular Disease Mechanisms and Nucleic Acid Therapeutics in Persistent Residual HIV Infection
- R01AI177265: Determinants of HIV-1 innate immune sensing and its role in shaping the lymphoid environment
Previous Completed Funding
Principal Investigator:
- R21MH129205: HIV innate sensing in glial cells and inflammation
- K22 AI140963: Direct live-cell visualization and quantification of interactions between infectious HIV particles in primary target cells
- CHEETAH Center Development Award: Study of the early-steps of the HIV replication cycle of infectious HIV particles (Sub-contract from P50 AI150464)
Co-Investigator:
- R01AI150998: Functionally Defining HIV-Host Interactions During the Early HIV-1 Lifecycle
Our team
- David Gagliardi, IBS MS Student
- Stephanie Gambut, Research Lab Tech 3
- Charia McKee, PhD, Postdoctoral Fellow
- James Szczerkowski, Research Scientist
- Elizabeth Zambrano, IBS MS Student
- Janet Zayas, PhD, Instructor
- Li Zhang, PhD, Postdoctoral Fellow
Contact us
We welcome inquiries about our research, collaborations and funding. Please contact João Mamede, PhD.