Modulation of HIV Pathogenesis and T-cell Signaling by HIV-1 Nef

Saxena, Shailendra K.; Shrivastava, Gaurav; Tiwari, Sneham; Swamy, ML Arvinda; Nair, Madhavan

doi:10.2217/fvl.12.42

Cited by 7 publications

(4 citation statements)

References 121 publications

(94 reference statements)

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“…Decreased α-enolase (ENO1) would lead to decreased T-cell migration. Inhibition of T-cell migration would protect the infected cells from host immunological attack and help in immune evasion [ 53 – 57 ]. The decreased energy state of infected T-cell leading to inhibition of their migration goes in agreement with the observed downregulation of α-enolase (ENO1) and VDAC1.…”

Section: Discussionmentioning

confidence: 99%

Proteomic Profiling of SupT1 Cells Reveal Modulation of Host Proteins by HIV-1 Nef Variants

et al. 2015

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Nef is an accessory viral protein that promotes HIV-1 replication, facilitating alterations in cellular pathways via multiple protein-protein interactions. The advent of proteomics has expanded the focus on better identification of novel molecular pathways regulating disease progression. In this study, nef was sequenced from randomly selected patients, however, sequence variability identified did not elicited any specific mutation that could have segregated HIV-1 patients in different stages of disease progression. To explore the difference in Nef functionality based on sequence variability we used proteomics approach. Proteomic profiling was done to compare the effect of Nef variants in host cell protein expression. 2DGE in control and Nef transfected SupT1 cells demonstrated several differentially expressed proteins. Fourteen protein spots were detected with more than 1.5 fold difference. Significant down regulation was seen in six unique protein spots in the Nef treated cells. Proteins were identified as Cyclophilin A, EIF5A-1 isoform B, Rho GDI 1 isoform a, VDAC1, OTUB1 and α-enolase isoform 1 (ENO1) through LC-MS/MS. The differential expression of the 6 proteins was analyzed by Real time PCR, Western blotting and Immunofluorescence studies with two Nef variants (RP14 and RP01) in SupT1 cells. There was contrasting difference between the effect of these Nef variants upon the expression of these six proteins. Downregulation of α-enolase (ENO1), VDAC1 and OTUB1 was more significant by Nef RP01 whereas Cyclophilin A and RhoGDI were found to be more downregulated by Nef RP14. This difference in Nef variants upon host protein expression was also studied through a site directed mutant of Nef RP01 (55AAAAAAA61) and the effect was found to be reversed. Deciphering the role of these proteins mediated by Nef variants will open a new avenue of research in understanding Nef mediated pathogenesis. Overall study determines modulation of cellular protein expression in T cells by HIV-1 Nef variants.

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Section: Discussionmentioning

confidence: 99%

Proteomic Profiling of SupT1 Cells Reveal Modulation of Host Proteins by HIV-1 Nef Variants

et al. 2015

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“…Pathogenesis of HIV is, in part, determined by Nef protein, myristoylated virulence factor abrogating immunologic synapses within infected CD4 + T cells. 174 While the exact effects of Nef on T-cell antigen receptor signaling remain controversial, 174 Nef protein may have pleiotropic effects on mitochondria. In human bronchial epithelial cells (BEAS-2B) stably expressing Nef, mitochondria caused autophagy.…”

Section: Mitochondrial Dynamics Beyond Opa1 and Drp1mentioning

confidence: 99%

Connection Between HIV and Mitochondria in Cardiovascular Disease and Implications for Treatments

Hinton,

N’jai,

Vue

et al. 2024

Circulation Research

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HIV infection and antiretroviral therapy alter mitochondrial function, which can progressively lead to mitochondrial damage and accelerated aging. The interaction between persistent HIV reservoirs and mitochondria may provide insight into the relatively high rates of cardiovascular disease and mortality in persons living with HIV. In this review, we explore the intricate relationship between HIV and mitochondrial function, highlighting the potential for novel therapeutic strategies in the context of cardiovascular diseases. We reflect on mitochondrial dynamics, mitochondrial DNA, and mitochondrial antiviral signaling protein in the context of HIV. Furthermore, we summarize how toxicities related to early antiretroviral therapy and current highly active antiretroviral therapy can contribute to mitochondrial dysregulation, chronic inflammation, and poor clinical outcomes. There is a need to understand the mechanisms and develop new targeted therapies. We further consider current and potential future therapies for HIV and their interplay with mitochondria. We reflect on the next-generation antiretroviral therapies and HIV cure due to the direct and indirect effects of HIV persistence, associated comorbidities, coinfections, and the advancement of interdisciplinary research fields. This includes exploring novel and creative approaches to target mitochondria for therapeutic intervention.

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“…Nef proteins are not directly involved in the viral replication, but they play essential roles in viral pathogenesis at both early and late phases. The functions of Nef in disease progression has been extensively reviewed [ 47 , 48 , 49 , 50 ]. Nef is a pathogenic factor that is expressed early in the viral life cycle [ 48 ].…”

Section: Targeting Hiv-1 Intracellular Proteins As Therapeutic Tarmentioning

confidence: 99%

“…The functions of Nef in disease progression has been extensively reviewed [ 47 , 48 , 49 , 50 ]. Nef is a pathogenic factor that is expressed early in the viral life cycle [ 48 ]. The primary roles of Nef in the viral pathogenesis include CD4 downregulation, MHC class-I downregulation, CD28 downregulation, T-cell activation, and CD8αβ downregulation [ 51 ].…”

Section: Targeting Hiv-1 Intracellular Proteins As Therapeutic Tarmentioning

confidence: 99%

Review of Current Cell-Penetrating Antibody Developments for HIV-1 Therapy

Nordin¹,

Teow

2018

Molecules

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The discovery of highly active antiretroviral therapy (HAART) in 1996 has significantly reduced the global mortality and morbidity caused by the acquired immunodeficiency syndrome (AIDS). However, the therapeutic strategy of HAART that targets multiple viral proteins may render off-target toxicity and more importantly results in drug-resistant escape mutants. These have been the main challenges for HAART and refinement of this therapeutic strategy is urgently needed. Antibody-mediated treatments are emerging therapeutic modalities for various diseases. Most therapeutic antibodies have been approved by Food and Drug Administration (FDA) mainly for targeting cancers. Previous studies have also demonstrated the promising effect of therapeutic antibodies against HIV-1, but there are several limitations in this therapy, particularly when the viral targets are intracellular proteins. The conventional antibodies do not cross the cell membrane, hence, the pathogenic intracellular proteins cannot be targeted with this classical therapeutic approach. Over the years, the advancement of antibody engineering has permitted the therapeutic antibodies to comprehensively target both extra- and intra-cellular proteins in various infections and diseases. This review aims to update on the current progress in the development of antibody-based treatment against intracellular targets in HIV-1 infection. We also attempt to highlight the challenges and limitations in the development of antibody-based therapeutic modalities against HIV-1.

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Modulation of HIV Pathogenesis and T-cell Signaling by HIV-1 Nef

Cited by 7 publications

References 121 publications

Proteomic Profiling of SupT1 Cells Reveal Modulation of Host Proteins by HIV-1 Nef Variants

Proteomic Profiling of SupT1 Cells Reveal Modulation of Host Proteins by HIV-1 Nef Variants

Connection Between HIV and Mitochondria in Cardiovascular Disease and Implications for Treatments

Review of Current Cell-Penetrating Antibody Developments for HIV-1 Therapy

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