Mannose Receptor 1 Restricts HIV Particle Release from Infected Macrophages

Sukegawa, Sayaka; Miyagi, Eri; Bouamr, Fadila; Farkašová, Helena; Strebel, Klaus

doi:10.1016/j.celrep.2017.12.085

Cited by 27 publications

(37 citation statements)

References 46 publications

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“…As recently reported by Sukegawa at al. (2018) with reference to HIV-1, MRC1 inhibits virus release and mediates HIV retention on the surface of virus-producing cells, thus causing a reduction in the progression of infection [ 53 ]. To the best of our knowledge, the possible involvement of MRC1 in the HCMV replication cycle has never been investigated.…”

Section: Resultsmentioning

confidence: 99%

Extracellular Vesicles in Human Preterm Colostrum Inhibit Infection by Human Cytomegalovirus In Vitro

et al. 2020

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Breast milk is a complex biofluid that nourishes infants, supports their growth and protects them from diseases. However, at the same time, breastfeeding is a transmission route for human cytomegalovirus (HCMV), with preterm infants being at a great risk of congenital disease. The discrepancy between high HCMV transmission rates and the few reported cases of infants with severe clinical illness is likely due to the protective effect of breast milk. The aim of this study was to investigate the anti-HCMV activity of human preterm colostrum and clarify the role of colostrum-derived extracellular vesicles (EVs). Preterm colostrum samples were collected and the EVs were purified and characterized. The in vitro anti-HCMV activity of both colostrum and EVs was tested against HCMV, and the viral replication step inhibited by colostrum-purified EVs was examined. We investigated the putative role EV surface proteins play in impairing HCMV infection using shaving experiments and proteomic analysis. The obtained results confirmed the antiviral action of colostrum against HCMV and demonstrated a remarkable antiviral activity of colostrum-derived EVs. Furthermore, we demonstrated that EVs impair the attachment of HCMV to cells, with EV surface proteins playing a role in mediating this action. These findings contribute to clarifying the mechanisms that underlie the protective role of human colostrum against HCMV infection.

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Section: Resultsmentioning

confidence: 99%

Extracellular Vesicles in Human Preterm Colostrum Inhibit Infection by Human Cytomegalovirus In Vitro

et al. 2020

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“…Thus, we could not exclude the hypothesis that Vpu interferes with another cellular partner to regulate the VCCs' size. Interestingly, several additional factors, such as Siglec-1 and mannose receptor 1, have been described to tether virus and favor their sequestration in MDMs (17,63). Moreover, several studies report that Vpu downregulates the tetraspanins CD63, CD81, and CD82 that are found enriched in VCCs (64)(65)(66).…”

Section: Discussionmentioning

confidence: 99%

Contribution of the Cytoplasmic Determinants of Vpu to the Expansion of Virus-Containing Compartments in HIV-1-Infected Macrophages

Leymarie

Lepont

Versapuech

et al. 2019

J Virol

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HIV-1 infection of macrophages leads to the sequestration of newly formed viruses in intracellular plasma membrane-connected structures termed virus-containing compartments (VCCs), where virions remain infectious and hidden from immune surveillance. The cellular restriction factor bone marrow stromal cell antigen 2 (BST2), which prevents HIV-1 dissemination by tethering budding viral particles at the plasma membrane, can be found in VCCs. The HIV-1 accessory protein Vpu counteracts the restriction factor BST2 by downregulating its expression and removing it from viral budding sites. Numerous studies described these Vpu countermeasures in CD4 ϩ T cells or model cell lines, but the interplay between Vpu and BST2 in VCC formation and HIV-1 production in macrophages is less explored. Here, we show that Vpu expression in HIV-1-infected macrophages enhances viral release. This effect is related to Vpu's ability to circumvent BST2 antiviral activity. We show that in absence of Vpu, BST2 is enriched in VCCs and colocalizes with capsid p24, whereas Vpu expression significantly reduces the presence of BST2 in these compartments. Furthermore, our data reveal that BST2 is dispensable for the formation of VCCs and that Vpu expression impacts the volume of these compartments. This Vpu activity partly depends on BST2 expression and requires the integrity of the Vpu transmembrane domain, the dileucine-like motif E 59 XXXLV 64 and phosphoserines 52 and 56 of Vpu. Altogether, these results highlight that Vpu controls the volume of VCCs and promotes HIV-1 release from infected macrophages. IMPORTANCE HIV-1 infection of macrophages leads to the sequestration of newly formed viruses in virus-containing compartments (VCCs), where virions remain infectious and hidden from immune surveillance. The restriction factor BST2, which prevents HIV-1 dissemination by tethering budding viral particles, can be found in VCCs. The HIV-1 Vpu protein counteracts BST2. This study explores the interplay between Vpu and BST2 in the viral protein functions on HIV-1 release and viral particle sequestration in VCCs in macrophages. The results show that Vpu controls the volume of VCCs and favors viral particle release. These Vpu functions partly depend on Vpu's ability to antagonize BST2. This study highlights that the transmembrane domain of Vpu and two motifs of the Vpu cytoplasmic domain are required for these functions. These motifs were notably involved in the control of the volume of VCCs by Vpu but were dispensable for the prevention of the specific accumulation of BST2 in these structures.

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“…Klaus Strebel (National Institute of Allergy and Infectious Diseases, NIH) described his work on the role of human mannose receptor (hMRC1) in antagonizing lentiviral replication [ 51 ]. This factor functions in macrophages to inhibit the detachment of budded virions from the cell surface in a manner much like tetherin.…”

Section: Env Trafficking and Incorporationmentioning

confidence: 99%

“…This factor functions in macrophages to inhibit the detachment of budded virions from the cell surface in a manner much like tetherin. Strebel’s group showed that the HIV-1 AD8 strain counteracts the effect of hMRC1 by reducing its expression via transcriptional silencing [ 51 ]. hMRC1 directly binds all of the HIV-1 Env isolates tested, but the connection between Env and hMRC1 binding remains unclear, as the release of VLPs not bearing HIV-1 Env glycoproteins is still inhibited by hMRC1 [ 51 ].…”

Section: Env Trafficking and Incorporationmentioning

confidence: 99%

“…Strebel’s group showed that the HIV-1 AD8 strain counteracts the effect of hMRC1 by reducing its expression via transcriptional silencing [ 51 ]. hMRC1 directly binds all of the HIV-1 Env isolates tested, but the connection between Env and hMRC1 binding remains unclear, as the release of VLPs not bearing HIV-1 Env glycoproteins is still inhibited by hMRC1 [ 51 ]. In addition to inhibiting the virus release, hMRC1 can also reduce the particle infectivity in an Env- and strain-dependent manner.…”

Section: Env Trafficking and Incorporationmentioning

confidence: 99%

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Meeting Review: 2018 International Workshop on Structure and Function of the Lentiviral gp41 Cytoplasmic Tail

Fernandez

Freed

2018

Viruses

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Recent developments in defining the role of the lentiviral envelope glycoprotein (Env) cytoplasmic tail (CT) in Env trafficking and incorporation into virus particles have advanced our understanding of viral replication and transmission. To stimulate additional progress in this field, the two-day International Workshop on Structure and Function of the Lentiviral gp41 Cytoplasmic Tail, co-organized by Eric Freed and James Hoxie, was held at the National Cancer Institute in Frederick, MD (26–27 April 2018). The meeting served to bring together experts focused on the role of gp41 in HIV replication and to discuss the emerging mechanisms of CT-dependent trafficking, Env conformation and structure, host protein interaction, incorporation, and viral transmission. The conference was organized around the following three main hot topics in gp41 research: the role of host factors in CT-dependent Env incorporation, Env structure, and CT-mediated trafficking and transmission. This review highlights important topics and the advances in gp41 research that were discussed during the conference.

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Mannose Receptor 1 Restricts HIV Particle Release from Infected Macrophages

Cited by 27 publications

References 46 publications

Extracellular Vesicles in Human Preterm Colostrum Inhibit Infection by Human Cytomegalovirus In Vitro

Extracellular Vesicles in Human Preterm Colostrum Inhibit Infection by Human Cytomegalovirus In Vitro

Contribution of the Cytoplasmic Determinants of Vpu to the Expansion of Virus-Containing Compartments in HIV-1-Infected Macrophages

Meeting Review: 2018 International Workshop on Structure and Function of the Lentiviral gp41 Cytoplasmic Tail

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