Productive HIV-1 infection of tissue macrophages by fusion with infected CD4+ T cells

Mascarau, Rémi; Woottum, Marie; Fromont, Léa; Gence, Rémi; Cantaloube-Ferrieu, Vincent; Vahlas, Zoï; Lévêque, Kevin; Bertrand, Florent; Beunon, Thomas; Métais, Arnaud; Costa, Hicham El; Jabrane‐Ferrat, Nabila; Gallois, Yohan; Guibert, Nicolas; Davignon, J.; Favre, Gilles; Maridonneau‐Parini, Isabelle; Poincloux, Renaud; Lagane, Bernard; Bénichou, Serge; Raynaud-Messina, Brigitte; Vérollet, Christel

doi:10.1083/jcb.202205103

Cited by 9 publications

(6 citation statements)

References 83 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Also, the cellular environment generated after macrophage infection with lab-adapted or T/F HIV strains can enhance infection of resting CD4+ T cells (19) and can even skew the differentiation of activated CD4+ T cells into more permissive profiles (20). Vice versa, it is well established that HIV-1 infected CD4+ T cells transmit HIV-1 to macrophages through the virological synapse, direct cell-to-cell contact and even via phagocytosis and fusion with infected CD4+ T cells (56,(58)(59)(60).…”

Section: Discussionmentioning

confidence: 99%

CD4+ T cells facilitate replication of primary HIV-1 strains in macrophages and formation of macrophage internal virus-containing compartments

Montero,

Leyens,

Meckes

et al. 2024

Preprint

View full text Add to dashboard Cite

HIV-1 infects CD4+ T cells and macrophages. However, replication of HIV-1 in these cell types is highly variable and may depend on the use of CCR5 as a co-receptor. In addition, there is internal accumulation of infectious HIV-1 in so-called virus-containing compartments of macrophages (VCCs). VCCs are thought to represent a persistent viral reservoir that is shielded from the antiviral immune response. To date, VCC formation has only been studied in lab-adapted HIV-1 and it is unknown whether VCCs play a role in the replication of primary HIV-1 strains. Furthermore, although macrophages transmit HIV-1 from VCCs to CD4+ T cells, it is unknown whether T cells have an impact on VCC formation. We analyzed the ability of primary and lab-adapted HIV-1 to replicate in macrophages, the effect of coculture with non-infected CD4+ T cells and the extent of VCC formation. Although differentially, all HIV-1 strains replicated in CD4+ T cells, whereas only lab-adapted HIV-1 replicated in macrophages. Strikingly, replication of patient-derived HIV-1 in macrophages was enhanced by coculture with non-infected CD4+ T cells and correlated with VCC formation. In conclusion, non-infected CD4+ T cells facilitate the replication of primary HIV-1 strains in macrophages and the formation of VCCs appears to be a proxy for this phenotype. Our study suggests an essential role for VCCs in the replication of patient-derived HIV-1 in macrophages, which is fueled by non-infected CD4+ T cells. Furthermore, our findings call for strategies to specifically disrupt VCC formation in order to eliminate the HIV-1 reservoir in macrophages.

show abstract

Section: Discussionmentioning

confidence: 99%

CD4+ T cells facilitate replication of primary HIV-1 strains in macrophages and formation of macrophage internal virus-containing compartments

Montero,

Leyens,

Meckes

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…Activated macrophages produce proinflammatory cytokines, i.e., tumour necrosis factor-alpha (TNFα) (Lee et al, 2021;Lechner et al, 2022;Tanito et al, 2023) and interleukin-12 (IL-12) (Luo et al, 2022;Pfirschke et al, 2022), to promote inflammation and activate other immune cells. Macrophages also process and present antigens to T cells via major histocompatibility complex (MHC) molecules aiding adaptive immune response (Mascarau et al, 2023;van Elsas et al, 2023). Interestingly, tissue-specific macrophages display unique functions.…”

Section: ) Debrismentioning

confidence: 99%

Tumour-associated macrophages: versatile players in the tumour microenvironment

Ji,

Chan,

Chan

et al. 2023

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Tumour-Associated Macrophages (TAMs) are one of the pivotal components of the tumour microenvironment. Their roles in the cancer immunity are complicated, both pro-tumour and anti-cancer activities are reported, including not only angiogenesis, extracellular matrix remodeling, immunosuppression, drug resistance but also phagocytosis and tumour regression. Interestingly, TAMs are highly dynamic and versatile in solid tumours. They show anti-cancer or pro-tumour activities, and interplay between the tumour microenvironment and cancer stem cells and under specific conditions. In addition to the classic M1/M2 phenotypes, a number of novel dedifferentiation phenomena of TAMs are discovered due to the advanced single-cell technology, e.g., macrophage-myofibroblast transition (MMT) and macrophage-neuron transition (MNT). More importantly, emerging information demonstrated the potential of TAMs on cancer immunotherapy, suggesting by the therapeutic efficiency of the checkpoint inhibitors and chimeric antigen receptor engineered cells based on macrophages. Here, we summarized the latest discoveries of TAMs from basic and translational research and discussed their clinical relevance and therapeutic potential for solid cancers.

show abstract

“…In line with this observation, macrophages express the HIV-1 receptor CD4 and coreceptors CCR5 and CXCR4 and support productive HIV-1 infection in vitro [22][23][24][25][26][27] . Other mechanisms of infection in macrophages include cell-to-cell transmission, fusion with, or phagocytosis of infected CD4 + T-cells [28][29][30][31] . Of note, the expression of do-not-eat-me signals is modulated by HIV-1 in CD4 + T-cells, thus facilitating phagocytosis by macrophages for subsequent productive infection 32 .…”

Section: Introductionmentioning

confidence: 99%

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

Dias,

Cattin,

Goulet

et al. 2023

Preprint

View full text Add to dashboard Cite

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:

show abstract

Productive HIV-1 infection of tissue macrophages by fusion with infected CD4+ T cells

Cited by 9 publications

References 83 publications

CD4+ T cells facilitate replication of primary HIV-1 strains in macrophages and formation of macrophage internal virus-containing compartments

CD4+ T cells facilitate replication of primary HIV-1 strains in macrophages and formation of macrophage internal virus-containing compartments

Tumour-associated macrophages: versatile players in the tumour microenvironment

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

Contact Info

Product

Resources

About