PLA2G1B is involved in CD4 anergy and CD4 lymphopenia in HIV-infected patients

Pothlichet, Julien; Rose, Thierry; Bugault, Florence; Jeammet, Louise; Meola, Annalisa; Haouz, Ahmed; Saul, F.A.; Geny, David; Alcamí, José; Ruiz‐Mateos, Ezequiel; Teyton, Luc; Lambeau, Gérard; Thèze, Jacques

doi:10.1172/jci131842

Cited by 26 publications

(39 citation statements)

References 59 publications

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“…Pothlichet et al [ 18 ] reported that sPLA 2 -IB is involved in CD4 + T cell lymphopenia in patients infected with human immunodeficiency virus (HIV). sPLA 2 -IB, in synergy with the HIV gp41 envelope protein, induces CD4 + T cell anergy, inhibiting the responses to IL-2, IL-4, and IL-7 as well as activation, proliferation, and survival of CD4 + T cells.…”

Section: The Spla 2 Familymentioning

confidence: 99%

Updating Phospholipase A2 Biology

2020

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The phospholipase A2 (PLA2) superfamily contains more than 50 enzymes in mammals that are subdivided into several distinct families on a structural and biochemical basis. In principle, PLA2 has the capacity to hydrolyze the sn-2 position of glycerophospholipids to release fatty acids and lysophospholipids, yet several enzymes in this superfamily catalyze other reactions rather than or in addition to the PLA2 reaction. PLA2 enzymes play crucial roles in not only the production of lipid mediators, but also membrane remodeling, bioenergetics, and body surface barrier, thereby participating in a number of biological events. Accordingly, disturbance of PLA2-regulated lipid metabolism is often associated with various diseases. This review updates the current state of understanding of the classification, enzymatic properties, and biological functions of various enzymes belonging to the PLA2 superfamily, focusing particularly on the novel roles of PLA2s in vivo.

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Section: The Spla 2 Familymentioning

confidence: 99%

Updating Phospholipase A2 Biology

2020

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“…However, evidence showed that HIV pathogenesis cannot be solely explained by the direct viral killing hypothesis as uninfected CD4+ T cells have a shortened half-life by cellular viral contact affecting IL-7 signalization ( 99 ). Another explanation is phospholipase A2 group IB (PLA2G1B) which synergizes with the HIV gp41 envelope protein and targets the CD4+ T cell surface, leading to CD4+ T cell unresponsiveness (anergy) ( 100 ).…”

Section: Mechanisms Of Cd4+ T Cell Lymphopeniamentioning

confidence: 99%

Sharing CD4+ T Cell Loss: When COVID-19 and HIV Collide on Immune System

et al. 2020

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COVID-19 is a distinctive infection characterized by elevated inter-human transmission and presenting from absence of symptoms to severe cytokine storm that can lead to dismal prognosis. Like for HIV, lymphopenia and drastic reduction of CD4+ T cell counts in COVID-19 patients have been linked with poor clinical outcome. As CD4+ T cells play a critical role in orchestrating responses against viral infections, important lessons can be drawn by comparing T cell response in COVID-19 and in HIV infection and by studying HIV-infected patients who became infected by SARS-CoV-2. We critically reviewed host characteristics and hyper-inflammatory response in these two viral infections to have a better insight on the large difference in clinical outcome in persons being infected by SARS-CoV-2. The better understanding of mechanism of T cell dysfunction will contribute to the development of targeted therapy against severe COVID-19 and will help to rationally design vaccine involving T cell response for the long-term control of viral infection.

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“…Thus, fewer CD4 T-cells available to bind circulating cytokines (lower consumption) can contribute, at least partially, to increased levels of IL-7 and IL-15 in ISRs. Of note, a recent study showed that phospholipase A2 group IB (PLA2G1B) synergized with the HIV gp41 envelope protein to inhibit CD4+ T-cell responses to IL-7 by promoting the formation of abnormal membrane microdomains which trap and inactivate IL-7R [75]. Furthermore, considering the key role of CM CD4 T-cells in maintaining homeostasis of the overall CD4 T-cell compartment [32], the higher levels of CM T-cells infection we described in ISR may prevent adequate repopulation of all CD4 memory cells despite higher cytokine levels.…”

Section: Discussionmentioning

confidence: 99%

Increased homeostatic cytokines and stability of HIV-infected memory CD4 T-cells identify individuals with suboptimal CD4 T-cell recovery on-ART

et al. 2021

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Clinical outcomes are inferior for individuals with HIV having suboptimal CD4 T-cell recovery during antiretroviral therapy (ART). We investigated if the levels of infection and the response to homeostatic cytokines of CD4 T-cell subsets contributed to divergent CD4 T-cell recovery and HIV reservoir during ART by studying virologically-suppressed immunologic responders (IR, achieving a CD4 cell count >500 cells/μL on or before two years after ART initiation), and virologically-suppressed suboptimal responders (ISR, did not achieve a CD4 cell count >500 cells/μL in the first two years after ART initiation). Compared to IR, ISR demonstrated higher levels of HIV-DNA in naïve, central (CM), transitional (TM), and effector (EM) memory CD4 T-cells in blood, both pre- and on-ART, and specifically in CM CD4 T-cells in LN on-ART. Furthermore, ISR had higher pre-ART plasma levels of IL-7 and IL-15, cytokines regulating T-cell homeostasis. Notably, pre-ART PD-1 and TIGIT expression levels were higher in blood CM and TM CD4 T-cells for ISR; this was associated with a significantly lower fold-changes in HIV-DNA levels between pre- and on-ART time points exclusively on CM and TM T-cell subsets, but not naïve or EM T-cells. Finally, the frequency of CM CD4 T-cells expressing PD-1 or TIGIT pre-ART as well as plasma levels of IL-7 and IL-15 predicted HIV-DNA content on-ART. Our results establish the association between infection, T-cell homeostasis, and expression of PD-1 and TIGIT in long-lived CD4 T-cell subsets prior to ART with CD4 T-cell recovery and HIV persistence on-ART.

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PLA2G1B is involved in CD4 anergy and CD4 lymphopenia in HIV-infected patients

Cited by 26 publications

References 59 publications

Updating Phospholipase A2 Biology

Updating Phospholipase A2 Biology

Sharing CD4+ T Cell Loss: When COVID-19 and HIV Collide on Immune System

Increased homeostatic cytokines and stability of HIV-infected memory CD4 T-cells identify individuals with suboptimal CD4 T-cell recovery on-ART

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