Joseph Varriale
A5056855583- HIV Research and Treatment
- HIV/AIDS drug development and treatment
- Cytomegalovirus and herpesvirus research
- Immune Cell Function and Interaction
- Bacteriophages and microbial interactions
- HIV/AIDS Research and Interventions
- vaccines and immunoinformatics approaches
- CRISPR and Genetic Engineering
- T-cell and B-cell Immunology
Johns Hopkins Medicine
2020-2024
Johns Hopkins University
2020-2024
National Institute of Allergy and Infectious Diseases
2020
National Institutes of Health
2020
HIV-1 persists in a latent reservoir resting CD4+ T cells despite antiretroviral therapy (ART). The decays slowly over the first seven years of ART (t1/2 = 44 months). However, whether decay continues with long-term is unclear. Recent integration site studies indicate gradual selection against inducible, intact proviruses, raising speculation that decades might allow treatment interruption without viral rebound. Therefore, we measured 42 people on (mean 22 years) using quantitative outgrowth...
Background. Antiretroviral therapy (ART) halts HIV-1 replication, decreasing viremia to below the detection limit of clinical assays. However, some individuals experience persistent nonsuppressible (NSV) originating from CD4+ T cell clones carrying infectious proviruses. Defective proviruses represent over 90% all persisting during ART and can express viral genes, but whether they cause NSV complicate management is unknown.
Significance In untreated individuals, HIV-1 evolves rapidly to escape the host immune responses. Viral replication can be effectively suppressed by antiretroviral therapy (ART). However, ART is not curative due persistence of latent virus in a stable reservoir resting CD4 + T cells, and viral rebound occurs if stopped. We show here that outgrowth significant fraction viruses persisting blocked antibody response. It important find ways induce antibodies or other responses block remaining viruses.
Background: A sterilizing cure of HIV-1 infection has been reported in 2 persons living with who underwent allogeneic hematopoietic stem cell transplantations from donors were homozygous for the CCR5Δ32 gene polymorphism. However, this considered elusive during natural infection. Objective: To evaluate persistent reservoir cells an elite controller undetectable viremia more than 8 years absence antiretroviral therapy. Design: Detailed investigation virologic and immunologic characteristics....
The vaccine elicitation of broadly neutralizing antibodies against HIV-1 is a long-sought goal. We previously reported the amino-terminal eight residues HIV-1-fusion peptide (FP8) - when conjugated to carrier protein, keyhole limpet hemocyanin (KLH) be capable inducing responses in animal models. However, KLH multi-subunit particle derived from natural source, and its manufacture as clinical product remains challenge. Here we report preclinical development recombinant tetanus toxoid heavy...
Reversing HIV-1 latency promotes killing of infected cells and is essential for cure strategies; however, no single reversing agent (LRA) or LRA combination have been shown to reduce latent reservoir size in persons living with (PLWH). Here, we describe an approach systematically identify combinations reactivate using genome-wide CRISPR screens. Screens on treated suboptimal concentrations can host genes whose knockout enhances viral gene expression. Therefore, inhibitors these should...
Summary The latent reservoir of HIV persists for decades in people living with (PWH) on antiretroviral therapy (ART). To determine if persistence arises from the natural dynamics memory CD4+ T cells harboring HIV, we compared clonal proviruses to that cell receptors (TCRβ) same PWH and HIV-seronegative people. We show dominance antigen-specific are similar but field’s understanding less clonally dominant is significantly limited by undersampling. demonstrate increasing clonality over time...