Dataset Information

Combined Effects of HLA-B*57/5801 Elite Suppressor CD8+ T Cells and NK Cells on HIV-1 Replication.

ABSTRACT: Elite controllers or suppressors (ES) are HIV-1 infected individuals who maintain undetectable viral loads without anti-retroviral therapy. The HLA-B*57 allele is overrepresented in ES suggesting a role for HIV-specific CD8+ T cells in immune control. Natural killer (NK) cells also play a role in controlling viral replication, and genetic studies demonstrate that specific combinations of killer cell immunoglobulin-like receptor (KIR) alleles and HLA subtypes including HLA-B*57 correlate with delayed progression to AIDS. While prior studies have shown that both HIV-specific CD8+ T cells and NK cells can inhibit viral replication in vitro, the interaction between these two effector cells has not been studied. We performed in vitro suppression assays using CD8+ T cells and NK cells from HLA-B*57 ES either alone or in combination with each other. We found no evidence of antagonism or synergy between the CD8+ T cells and NK cells, suggesting that they have independent mechanisms of inhibition in vitro. Our data has implications for combined immunotherapy with CD8+ T cells and NK cells in HIV cure strategies.

SUBMITTER: May ME

PROVIDER: S-EPMC7098910 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Publications

Combined Effects of HLA-B*57/5801 Elite Suppressor CD8+ T Cells and NK Cells on HIV-1 Replication.

May Megan E ME Pohlmeyer Christopher W CW Kwaa Abena K AK Mankowski Madeleine C MC Bailey Justin R JR Blankson Joel N JN

Frontiers in cellular and infection microbiology 20200320

Elite controllers or suppressors (ES) are HIV-1 infected individuals who maintain undetectable viral loads without anti-retroviral therapy. The HLA-B*57 allele is overrepresented in ES suggesting a role for HIV-specific CD8+ T cells in immune control. Natural killer (NK) cells also play a role in controlling viral replication, and genetic studies demonstrate that specific combinations of killer cell immunoglobulin-like receptor (KIR) alleles and HLA subtypes including HLA-B*57 correlate with del ...[more]

PMID: 32266164

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Project description:Elite controllers or suppressors (ES) are HIV-1-infected patients who maintain undetectable viral loads without antiretroviral therapy. The mechanism of control remains unclear, but the HLA-B*57 allele is overrepresented in cohorts of these patients. However, many HLA-B*57 patients develop progressive disease, and some studies have suggested that infection with defective viruses may be the cause of the lack of high levels of virus replication and disease progression in ES. We therefore performed a comprehensive comparative in vivo and in vitro characterization of viruses isolated from well-defined ES. For this purpose, we first performed full-genome sequence analysis and in vitro fitness assays on replication-competent isolates from HLA-B*57 ES and HLA-B*57 chronic progressors (CPs). Under our experimental conditions, we found that isolates from ES and CPs can replicate in vitro. However, since inherently these assays involve the use of unnaturally in vitro-activated cells, we also investigated the replication competence and pathogenic potential of these HIV isolates in vivo using humanized BLT mice. The results from these analyses demonstrate that virus isolates from ES are fully replication competent in vivo and can induce peripheral and systemic CD4 T cell depletion. These results provide the first direct in vivo evidence that viral fitness does not likely determine clinical outcome in HLA-B*57 patients and that elite suppressors can control replication-competent, fully pathogenic viruses. A better understanding of the immunological bases of viral suppression in ES will serve to inform novel approaches to preventive and therapeutic HIV vaccine design.Elite suppressors are HIV-1-infected patients who have undetectable levels of viremia despite not being on antiviral drugs. One of the most fundamental questions about this phenomenon involves the mechanism of control. To address this question, we isolated virus from elite suppressors and from HIV-1-infected patients who have the usual progressive disease course. We compared how well the isolates from the two groups of patients replicated in culture and in humanized mice. Our results suggest that elite suppressors are capable of controlling HIV-1 due to the possession of unique host factors rather than infection with defective virus.

Dataset Information

Combined Effects of HLA-B*57/5801 Elite Suppressor CD8+ T Cells and NK Cells on HIV-1 Replication.

Publications

Combined Effects of HLA-B*57/5801 Elite Suppressor CD8+ T Cells and NK Cells on HIV-1 Replication.

Similar Datasets

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