background and objectives: to enter the target cell, HIV-1 binds not only CD4 but also a co-receptor beta -chemokine receptor 5 (CCR5) or alpha chemokine receptor 4 (CXCR4). limited information is available on the impact of co-receptor usage on HIV-1 replication in monocyte-derived macrophages (MDM) and on the homeostasis of this important cellular reservoir. materials and methods: replication (measured by p24 production) of the CCR5-tropic 81A strain increased up to 10 days post-infection and then reached a plateau. conversely, the replication of the CXCR4-tropic NL4.3 strain (after an initial increase up to day 7) underwent a drastic decrease becoming almost undetectable after 10 days post-infection. the ability of CCR5-tropic and CXCR4-tropic strains to induce cell death in MDM was then evaluated. While for CCR5-tropic 81A the rate of apoptosis in MDM was comparable to uninfected MDM, the infection of CXCR4-tropic NL4.3 in MDM was associated with a rate of 14.3% of apoptotic cells at day 6 reaching a peak of 43.5% at day 10 post-infection. results: this suggests that the decrease in CXCR4-tropic strain replication in MDM can be due to their ability to induce cell death in MDM. the increase in apoptosis was paralleled with a 2-fold increase in the phosphorylated form of p38 compared to WT. furthermore, microarray analysis showed modulation of proapoptotic and cancer-related genes induced by CXCR4-tropic strains starting from 24 h after infection, whereas CCR5 viruses modulated the expression of genes not correlated with apoptotic-pathways. conclusions: In conclusion, CXCR4-tropic strains can induce a remarkable depletion of MDM. conversely, MDM can represent an important cellular reservoir for CCR5-tropic strains supporting the role of CCR5-usage in HIV-1 pathogenesis and as a pharmacological target to contribute to an HIV-1 cure.

Borrajo, A., Ranazzi, A., Pollicita, M., Concetta Bellocchi, M., Salpini, R., Mauro, M.v., et al. (2019). Different patterns of HIV-1 replication in MACROPHAGES is led by co-receptor usage. MEDICINA, 55(6) [10.3390/medicina55060297].

Different patterns of HIV-1 replication in MACROPHAGES is led by co-receptor usage

Pollicita M.;Concetta Bellocchi M.;Salpini R.;Ceccherini-Silberstein F.;Perno C. F.;Svicher V.;Aquaro S.
2019-01-01

Abstract

background and objectives: to enter the target cell, HIV-1 binds not only CD4 but also a co-receptor beta -chemokine receptor 5 (CCR5) or alpha chemokine receptor 4 (CXCR4). limited information is available on the impact of co-receptor usage on HIV-1 replication in monocyte-derived macrophages (MDM) and on the homeostasis of this important cellular reservoir. materials and methods: replication (measured by p24 production) of the CCR5-tropic 81A strain increased up to 10 days post-infection and then reached a plateau. conversely, the replication of the CXCR4-tropic NL4.3 strain (after an initial increase up to day 7) underwent a drastic decrease becoming almost undetectable after 10 days post-infection. the ability of CCR5-tropic and CXCR4-tropic strains to induce cell death in MDM was then evaluated. While for CCR5-tropic 81A the rate of apoptosis in MDM was comparable to uninfected MDM, the infection of CXCR4-tropic NL4.3 in MDM was associated with a rate of 14.3% of apoptotic cells at day 6 reaching a peak of 43.5% at day 10 post-infection. results: this suggests that the decrease in CXCR4-tropic strain replication in MDM can be due to their ability to induce cell death in MDM. the increase in apoptosis was paralleled with a 2-fold increase in the phosphorylated form of p38 compared to WT. furthermore, microarray analysis showed modulation of proapoptotic and cancer-related genes induced by CXCR4-tropic strains starting from 24 h after infection, whereas CCR5 viruses modulated the expression of genes not correlated with apoptotic-pathways. conclusions: In conclusion, CXCR4-tropic strains can induce a remarkable depletion of MDM. conversely, MDM can represent an important cellular reservoir for CCR5-tropic strains supporting the role of CCR5-usage in HIV-1 pathogenesis and as a pharmacological target to contribute to an HIV-1 cure.
2019
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/07 - MICROBIOLOGIA E MICROBIOLOGIA CLINICA
Settore MEDS-03/A - Microbiologia e microbiologia clinica
English
human immunodeficiency virus; monocyte-derived macrophages; α chemokine receptor 4; β-chemokine receptor 5; Anti-HIV Agents; DNA Fragmentation; HIV-1; Heterocyclic Compounds; Humans; Macrophages; Receptors, CCR5; Receptors, CXCR4
Borrajo, A., Ranazzi, A., Pollicita, M., Concetta Bellocchi, M., Salpini, R., Mauro, M.v., et al. (2019). Different patterns of HIV-1 replication in MACROPHAGES is led by co-receptor usage. MEDICINA, 55(6) [10.3390/medicina55060297].
Borrajo, A; Ranazzi, A; Pollicita, M; Concetta Bellocchi, M; Salpini, R; Mauro, Mv; Ceccherini-Silberstein, F; Perno, Cf; Svicher, V; Aquaro, S...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/238627
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