Gregory T. Gladkov
A5011751809- HIV Research and Treatment
- Immune Cell Function and Interaction
- HIV/AIDS drug development and treatment
- Immunotherapy and Immune Responses
- Viral-associated cancers and disorders
- HIV/AIDS Research and Interventions
- Cytomegalovirus and herpesvirus research
- Reproductive System and Pregnancy
- Innovative Microfluidic and Catalytic Techniques Innovation
Ragon Institute of MGH, MIT and Harvard
2022-2024
Brigham and Women's Hospital
2023-2024
HIV-1-infected cells that persist despite antiretroviral therapy (ART) are frequently considered "transcriptionally silent," but active viral gene expression may occur in some cells, challenging the concept of latency. Applying an assay for profiling transcriptional activity and chromosomal locations individual proviruses, we describe a global genomic epigenetic map transcriptionally silent proviral species evaluate their longitudinal evolution persons receiving suppressive ART. Using...
HIV-1 establishes a life-long reservoir of virally infected cells which cannot be eliminated by antiretroviral therapy (ART). Here, we demonstrate markedly altered viral profile long-term ART-treated individuals, characterized large clones intact proviruses preferentially integrated in heterochromatin locations, most prominently centromeric satellite/micro-satellite DNA. Longitudinal evaluations suggested that this specific configuration results from selection processes promote the...
Although gut and lymph node (LN) memory CD4 T cells represent major HIV simian immunodeficiency virus (SIV) tissue reservoirs, the study of role dendritic (DCs) in persistence has long been limited to blood due difficulties access lymphoid samples. In this study, we show that LN migratory resident DC subpopulations harbor distinct phenotypic transcriptomic profiles. Interestingly, both contain intact provirus inducible replication-competent despite expression antiviral restriction factor...
Background: Persistent controllers (PC) maintain antiretroviral-free HIV-1 control indefinitely over time while transient (TC) eventually lose virological control. It is essential to characterize the quality of HIV reservoir these phenotypes identify factors that lead progression and open new avenues in cure strategies. Methods: The characterization reservoir, from peripheral blood mononuclear cells, was performed using next-generation sequencing techniques, such as full-length individual...
Antiretroviral treatment (ART) initiation during the early stages of HIV-1 infection is associated with a higher probability maintaining drug-free viral control subsequent interruptions, for reasons that remain unclear. Using samples from randomized-controlled human clinical trial evaluating therapeutic vaccines, we here show ART commencement frequently accelerated and efficient selection genome-intact proviruses in repressive chromatin locations first year after initiation. This process was...
We evaluated the safety and viral rebound, after analytical treatment interruption (ATI), of vedolizumab ART in recent HIV-1 infection. used this model to analyze impact α4β7 on reservoir size. Participants started with monthly Vedolizumab infusions ATI was performed at week 24. Biopsies were obtained from ileum caecum baseline levels, reservoir, flow cytometry cell-sorting antibody competition experiments assayed. safe well-tolerated. No participant achieved undetectable viremia off 24...
While gut and lymph node (LN) memory CD4 T cells represent major HIV SIV tissue reservoirs, the study of role dendritic (DCs) in persistence has long been limited to blood due difficulties access lymphoid samples. In present study, we showed that LN migratory resident DC subpopulations harbored distinct phenotypic transcriptomic profiles. Interestingly, both contained intact provirus inducible replication competent despite expression anti-viral restriction factor SAMHD1. Notably, isolated...