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

Journal of Virology, Journal Year: 2025, Volume and Issue: unknown

Published: March 25, 2025

ABSTRACT HIV-1 replication in macrophages is highly variable with internal virus accumulation so-called virus-containing compartments (VCCs). VCCs represent a reservoir that shielded from the antiviral immune response. VCC formation has been studied lab-adapted HIV-1, but it not investigated whether primary strains induce VCCs. Furthermore, although transmit to CD4+ T cells, effect of cells on unknown. We analyzed ability and replicate macrophages, non-infected cell coculture, formation. All replicated whereas only efficiently macrophage monocultures. Coculture enhanced process associated increased dependent direct cell-to-cell contact. Broadly neutralizing antibodies differentially affected cell-mediated enhancement macrophages. CD4 antibody treatment phenocopied infection-promoting coculture. In conclusion, facilitate induction appears be proxy for this phenotype. are promoted by CD4- GP120-dependent manner. Our findings highlight critical role cell-macrophage interaction dynamics call strategies interfere order target IMPORTANCE Here, we focus intimate interplay between HIV-1-infected cells. Specifically, (VCCs) within which thought serve as viral sanctuaries reservoirs. Notably, were unable unless they cocultured leading replication. This suggests an essential facilitating data importance addressing latent also targeting achieve ultimate goal functional cure.

Language: Английский

The Role of Macrophage Migration Inhibitory Factor (MIF) and D-Dopachrome Tautomerase (D-DT/MIF-2) in Infections: A Clinical Perspective

Biomedicines, Journal Year: 2023, Volume and Issue: 12(1), P. 2 - 2

Published: Dec. 19, 2023

Macrophage migration inhibitory factor (MIF) and its homolog, D-dopachrome tautomerase (D-DT), are cytokines that play critical roles in the immune response to various infectious diseases. This review provides an overview of complex involvement MIF D-DT bacterial, viral, fungal, parasitic infections. The role different types infections is controversial, as it has either a protective function or host damage-enhancing depending on pathogen. Depending specific MIF, therapeutic options for MIF-targeting drugs arise. Human MIF-neutralizing antibodies, anti-parasite small molecule inhibitors MIF-blocking peptides, well administration exogenous activity-augmenting molecules have potential applications need be further explored future. In addition, been shown biomarker target sepsis. Further research needed unravel complexity diseases develop personalized approaches targeting these cytokines. Overall, comprehensive understanding could lead new strategies diagnosis, treatment, management

Language: Английский

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

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 24, 2024

ABSTRACT HIV-1 infects CD4+ T cells and macrophages. However, replication of in these cell types is highly variable may depend on the use CCR5 as a co-receptor. In addition, there internal accumulation infectious so-called virus-containing compartments macrophages (VCCs). VCCs are thought to represent persistent viral reservoir that shielded from antiviral immune response. To date, VCC formation has only been studied lab-adapted it unknown whether play role primary strains. Furthermore, although transmit cells, have an impact formation. We analyzed ability replicate macrophages, effect coculture with non-infected extent Although differentially, all strains replicated whereas Strikingly, patient-derived was enhanced by correlated conclusion, facilitate appears be proxy for this phenotype. Our study suggests essential which fueled cells. our findings call strategies specifically disrupt order eliminate IMPORTANCE Here we focus intimate interplay between infected Specifically, induce (VCCs) within serve sanctuaries macrophage reservoirs. Notably, were unable unless they cocultured leading increased replication. This facilitating data highlight importance not targeting latent T-cell reservoir, but also achieve ultimate goal functional cure.

Language: Английский