Galectin-3 facilitates cell-to-cell HIV-1 transmission by altering the composition of membrane lipid rafts in CD4 T cells

Wang, Sheng-Fan; Hung, Yu-Hsiang; Tsao, Che-Wei; Chiang, Chun; Teoh, Pak-Guan; Chiang, Meng-Lin; Lin, Wei-Yang; Hsu, Daniel K.; Jan, Hau-Ming; Lin, Hsiu-Chu; Lin, Chung-Wei; Liu, Fu‐Tong; Chen, Huan‐Yuan

doi:10.1093/glycob/cwac040

Cited by 3 publications

(5 citation statements)

References 86 publications

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“…At the opposite, ATRA decreased expression of BIRC2 (suppressor of HIV transcription) 113 , SERINC5 (restriction factor for HIV-1 release) 114 , RNASE1 (inhibitor of HIV-1 production) 115 , SOD2 (an integral component of the cellular antioxidant system) 116 , HDAC7 (suppressor of HIV transcription) 117 , and GSK3B (an inducer of zink-finger antiviral protein (ZAP) functions ) 118 (Figure 4A-B). Unexpectedly, genes encoding for positive regulators of HIV transcription ( TRIM32 119 , NCOA1 120 ) and virion production/release ( LGALS3 121 , FURIN 122 . Furthermore, HIC1 and TCF4/TCF7L2 123 (Figure 4A-B), two negative regulators of HIV transcription 124 , were upregulated by ATRA in MDMs.…”

Section: Resultsmentioning

confidence: 99%

Retinoic Acid Boosts HIV-1 Replication in MacrophagesviaCCR5/SAMHD1-Dependent and mTOR-Modulated Mechanisms

Dias,

Cattin,

Goulet

et al. 2023

Preprint

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The intestinal environment facilitates HIV-1 infectionviamechanisms involving the gut-homing elixir retinoic acid (RA), which transcriptionally reprograms CD4+T-cells for increased HIV-1 permissiveness. Consistently, colon-infiltrating CD4+T-cells carry replication-competent viral reservoirs in people living with HIV-1 (PLWH) receiving antiretroviral therapy (ART). Intriguingly, integrative infection in colon macrophages, a pool replenished by circulating monocytes, represents a rare event in ART-treated PLWH, thus questioning on HIV-1 permissiveness in gut-resident macrophages. Here, we demonstrate that RA significantly boosts R5 but not X4 HIV-1 replication in monocyte-derived macrophages (MDMs). RNA-Sequencing, Gene Set Variation Analysis, and HIV interactor NCBI database interrogation, revealed RA- mediated transcriptional reprogramming associated with metabolic/inflammatory processes and HIV-1 resistance/dependency factors. Functional validations pointed to mechanisms of RA action, including CCR5 upregulation and SAMHD1 phosphorylation under the control of mTOR. These results support a model in which intestinal MDM contribute to viral replication/dissemination before ART and upon treatment interruption in mTOR-sensitive manner.Figure 1:

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Section: Resultsmentioning

confidence: 99%

Retinoic Acid Boosts HIV-1 Replication in MacrophagesviaCCR5/SAMHD1-Dependent and mTOR-Modulated Mechanisms

Dias,

Cattin,

Goulet

et al. 2023

Preprint

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“…Another possibility is that Gals may directly interact with SARS-CoV-2 and subsequently influence its infectivity as illustrated for Gal-3 and Gal-9 in HIV infection ( 39 , 60 ). For example, the plasma levels of Gal-9 are correlated with the viral load in acute dengue virus ( 28 ) and HIV infections ( 30 ).…”

Section: Discussionmentioning

confidence: 99%

Analysis of SARS-CoV-2 isolates, namely the Wuhan strain, Delta variant, and Omicron variant, identifies differential immune profiles

Shahbaz,

Bozorgmehr,

et al. 2023

Microbiol Spectr

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There is an urgent need to better understand the impact of different severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants on immune response and disease dynamics to facilitate better intervention strategies. Here, we show that SARS-CoV-2 variants differentially affect host immune responses. The magnitude and quantity of cytokines and chemokines were comparable in those infected with the Wuhan strain and the Delta variant. However, individuals infected with the Omicron variant had significantly lower levels of these mediators. We also found an elevation of plasma galectins (Gal-3, Gal-8, and Gal-9) in infected individuals, in particular, in those with the original strain. Soluble galectins exert a proinflammatory role in COVID-19 pathogenesis. This was illustrated by their correlation with the plasma levels of sCD14, sCD163, enhanced TNF-α/IL-6 secretion, and increased SARS-CoV-2 infectivity in vitro . Moreover, we observed enhanced CD4 + and CD8 + T cell activation in Wuhan strain-infected individuals. Surprisingly, there was a more pronounced T cell activation in those infected with the Omicron in comparison to the Delta variant. In line with T cell activation status, we observed a more pronounced expansion of T cells expressing different co-inhibitory receptors in patients infected with the Wuhan strain, followed by the Omicron and Delta variants. Individuals infected with the Wuhan strain or the Omicron variant had a similar pattern of plasma soluble immune checkpoints. Our results imply that a milder innate immune response might be beneficial and protective in those infected with the Omicron variant. Our results provide a novel insight into the differential impact of SARS-CoV-2 variants on host immunity. IMPORTANCE There is a need to better understand how different SARS-CoV-2 variants influence the immune system and disease dynamics to facilitate the development of better vaccines and therapies. We compared immune responses in 140 SARS-CoV-2-infected individuals with the Wuhan strain, the Delta variant, or the Omicron variant. All these patients were admitted to the intensive care unit and were SARS-CoV-2 vaccination naïve. We found that SARS-CoV-2 variants differentially affect the host immune response. This was done by measuring soluble biomarkers in their plasma and examining different immune cells. Overall, we found that the magnitude of cytokine storm in individuals infected with the Wuhan strain or the Delta variant was greater than in those infected with the Omicron variant. In light of enhanced cytokine release syndrome in individuals infected with the Wuhan strain or the Delta variant, we believe that a milder innate immune response might be beneficial and protective in those infected with the Omicron variant.

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“…It functions via interacting intracellularly with Gag and the cellular ALG-2-interacting protein X (Alix), which are essential for viral budding and replication when new infectious virions are generated [42]. Additionally, Gal-3 plays a role in regulating virological synapse formation and facilitating intercellular HIV-1 transfer among CD4 + T cells, providing an alternative pathway for HIV-1 infection regulation [43]. Exosomes derived from HIV-1-infected dendritic cells with high Gal-3 expression have been found to facilitate HIV-1 infection and dissemination through fibronectin and Gal-3mediated cell fusion [40].…”

Section: Galectin-3 In Viral Assembly and Releasementioning

confidence: 99%

“…Galectin-3 plays a crucial role in the process of HIV-1 viral budding, which is the final stage of the viral replication cycle [42]. This stage involves the release of newly formed virus particles from infected host cells, contributing significantly to the spread of HIV-1 infection within the host and the progression of the disease [43]. Furthermore, Gal-3 is highly expressed in exosomes derived from HIV-1-infected dendritic cells, compared to those from uninfected cells [40].…”

Section: Galectin-3 and Hiv-1 Disseminationmentioning

confidence: 99%

“…Cell-to-cell transmission of HIV-1 is an efficient mode of viral dissemination, allowing the virus to bypass extracellular defenses and evade host immune responses. Galectin-3 has been implicated in facilitating this process, contributing to the spread of the virus within the host [43]. Virological synapses are specialized cell-cell junctions that enable direct transfer of HIV-1 particles from infected cells to uninfected target cells [85].…”

Section: Galectin-3 and Hiv-1 Disseminationmentioning

confidence: 99%

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The Pivotal Role of Galectin-3 in Viral Infection: A Multifaceted Player in Host–Pathogen Interactions

Stojanović

Milovanović

et al. 2023

IJMS

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Galectin-3 (Gal-3), a beta-galactoside-binding lectin, plays a pivotal role in various cellular processes, including immune responses, inflammation, and cancer progression. This comprehensive review aims to elucidate the multifaceted functions of Gal-3, starting with its crucial involvement in viral entry through facilitating viral attachment and catalyzing internalization. Furthermore, Gal-3 assumes significant roles in modulating immune responses, encompassing the activation and recruitment of immune cells, regulation of immune signaling pathways, and orchestration of cellular processes such as apoptosis and autophagy. The impact of Gal-3 extends to the viral life cycle, encompassing critical phases such as replication, assembly, and release. Notably, Gal-3 also contributes to viral pathogenesis, demonstrating involvement in tissue damage, inflammation, and viral persistence and latency elements. A detailed examination of specific viral diseases, including SARS-CoV-2, HIV, and influenza A, underscores the intricate role of Gal-3 in modulating immune responses and facilitating viral adherence and entry. Moreover, the potential of Gal-3 as a biomarker for disease severity, particularly in COVID-19, is considered. Gaining further insight into the mechanisms and roles of Gal-3 in these infections could pave the way for the development of innovative treatment and prevention options for a wide range of viral diseases.

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Galectin-3 facilitates cell-to-cell HIV-1 transmission by altering the composition of membrane lipid rafts in CD4 T cells

Cited by 3 publications

References 86 publications

Retinoic Acid Boosts HIV-1 Replication in MacrophagesviaCCR5/SAMHD1-Dependent and mTOR-Modulated Mechanisms

Retinoic Acid Boosts HIV-1 Replication in MacrophagesviaCCR5/SAMHD1-Dependent and mTOR-Modulated Mechanisms

Analysis of SARS-CoV-2 isolates, namely the Wuhan strain, Delta variant, and Omicron variant, identifies differential immune profiles

The Pivotal Role of Galectin-3 in Viral Infection: A Multifaceted Player in Host–Pathogen Interactions

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