Different Patterns of HIV-1 Replication in MACROPHAGES is Led by Co-Receptor Usage
AbstractBackground and objectives: To enter the target cell, HIV-1 binds not only CD4 but also a co-receptor β-chemokine receptor 5 (CCR5) or α 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. View Full-Text
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Borrajo, A.; Ranazzi, A.; Pollicita, M.; Bellocchi, M.C.; Salpini, R.; Mauro, M.V.; Ceccherini-Silberstein, F.; Perno, C.F.; Svicher, V.; Aquaro, S. Different Patterns of HIV-1 Replication in MACROPHAGES is Led by Co-Receptor Usage. Medicina 2019, 55, 297.
Borrajo A, Ranazzi A, Pollicita M, Bellocchi MC, Salpini R, Mauro MV, Ceccherini-Silberstein F, Perno CF, Svicher V, Aquaro S. Different Patterns of HIV-1 Replication in MACROPHAGES is Led by Co-Receptor Usage. Medicina. 2019; 55(6):297.Chicago/Turabian Style
Borrajo, Ana; Ranazzi, Alessandro; Pollicita, Michela; Bellocchi, Maria C.; Salpini, Romina; Mauro, Maria V.; Ceccherini-Silberstein, Francesca; Perno, Carlo F.; Svicher, Valentina; Aquaro, Stefano. 2019. "Different Patterns of HIV-1 Replication in MACROPHAGES is Led by Co-Receptor Usage." Medicina 55, no. 6: 297.
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