Single Cell Profiling Reveals PTEN Overexpression in Influenza-Specific B cells in Aging HIV-infected individuals on Anti-retroviral Therapy

Lesley R. de Armas, Suresh Pallikkuth, Li Pan, Stefano Rinaldi, Nicola Cotugno, Sarah Andrews, Rajendra Pahwa, Adrian B. McDermott, Paolo Palma, Savita G Pahwa

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Memory B cells (MBC) respond to secondary antigen challenge to protect against infection and to boost immunity following vaccinations. Despite effective treatment, chronic HIV infection disturbs MBCs by reducing numbers and altering functionality due to hyper-activation and increased apoptosis leading to suboptimal antibody responses against common infectious agents. We used single cell gene expression analysis to evaluate antigen-specific memory B cells in peripheral blood of virally-suppressed HIV-infected individuals and healthy controls stratified by serum H1N1 antibody response 3 weeks post-administration of the seasonal trivalent inactivated influenza vaccine. We used a fluorescent probe to isolate influenza H1N1-specific B cells and a multiplexed and targeted RT-PCR approach to measure expression levels of 96 genes involved in B cell activation and function. Gene profiling revealed a 4-gene predictive signature containing the phosphoinositide-3 kinase (PI3K) inhibitor, PTEN, for identifying antigen-specific MBC from HIV-infected individuals compared to healthy controls. Gene co-expression analysis showed that in addition to overexpression of PTEN, there was increased co-expression of type I interferon-associated genes with PTEN on single cell level in HIV compared to controls. This study highlights the persistent defects in MBC from HIV-infected individuals and points to the PI3K signaling pathway as a target for potential immune intervention.

Original languageEnglish (US)
Article number2482
JournalScientific reports
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2019

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Cell Aging
Human Influenza
B-Lymphocytes
HIV
1-Phosphatidylinositol 4-Kinase
Antigens
Genes
Antibody Formation
Therapeutics
Gene Expression
Interferon Type I
Inactivated Vaccines
Influenza Vaccines
Fluorescent Dyes
HIV Infections
Immunity
Vaccination
Apoptosis
Polymerase Chain Reaction
Infection

ASJC Scopus subject areas

  • General

Cite this

Single Cell Profiling Reveals PTEN Overexpression in Influenza-Specific B cells in Aging HIV-infected individuals on Anti-retroviral Therapy. / de Armas, Lesley R.; Pallikkuth, Suresh; Pan, Li; Rinaldi, Stefano; Cotugno, Nicola; Andrews, Sarah; Pahwa, Rajendra; McDermott, Adrian B.; Palma, Paolo; Pahwa, Savita G.

In: Scientific reports, Vol. 9, No. 1, 2482, 01.12.2019.

Research output: Contribution to journalArticle

de Armas, Lesley R. ; Pallikkuth, Suresh ; Pan, Li ; Rinaldi, Stefano ; Cotugno, Nicola ; Andrews, Sarah ; Pahwa, Rajendra ; McDermott, Adrian B. ; Palma, Paolo ; Pahwa, Savita G. / Single Cell Profiling Reveals PTEN Overexpression in Influenza-Specific B cells in Aging HIV-infected individuals on Anti-retroviral Therapy. In: Scientific reports. 2019 ; Vol. 9, No. 1.
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abstract = "Memory B cells (MBC) respond to secondary antigen challenge to protect against infection and to boost immunity following vaccinations. Despite effective treatment, chronic HIV infection disturbs MBCs by reducing numbers and altering functionality due to hyper-activation and increased apoptosis leading to suboptimal antibody responses against common infectious agents. We used single cell gene expression analysis to evaluate antigen-specific memory B cells in peripheral blood of virally-suppressed HIV-infected individuals and healthy controls stratified by serum H1N1 antibody response 3 weeks post-administration of the seasonal trivalent inactivated influenza vaccine. We used a fluorescent probe to isolate influenza H1N1-specific B cells and a multiplexed and targeted RT-PCR approach to measure expression levels of 96 genes involved in B cell activation and function. Gene profiling revealed a 4-gene predictive signature containing the phosphoinositide-3 kinase (PI3K) inhibitor, PTEN, for identifying antigen-specific MBC from HIV-infected individuals compared to healthy controls. Gene co-expression analysis showed that in addition to overexpression of PTEN, there was increased co-expression of type I interferon-associated genes with PTEN on single cell level in HIV compared to controls. This study highlights the persistent defects in MBC from HIV-infected individuals and points to the PI3K signaling pathway as a target for potential immune intervention.",
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