Different Patterns of HIV-1 Replication in MACROPHAGES is Led by Co-Receptor Usage
<i>Background and objectives:</i> 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 monoc...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2019-06-01
|
| Series: | Medicina |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1010-660X/55/6/297 |
| _version_ | 1797717194721722368 |
|---|---|
| author | Ana Borrajo Alessandro Ranazzi Michela Pollicita Maria Concetta Bellocchi Romina Salpini Maria Vittoria Mauro Francesca Ceccherini-Silberstein Carlo Federico Perno Valentina Svicher Stefano Aquaro |
| author_facet | Ana Borrajo Alessandro Ranazzi Michela Pollicita Maria Concetta Bellocchi Romina Salpini Maria Vittoria Mauro Francesca Ceccherini-Silberstein Carlo Federico Perno Valentina Svicher Stefano Aquaro |
| author_sort | Ana Borrajo |
| collection | DOAJ |
| description | <i>Background and objectives:</i> 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. <i>Materials and Methods:</i> 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. <i>Results:</i> 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. <i>Conclusions:</i> 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. |
| first_indexed | 2024-03-12T08:32:54Z |
| format | Article |
| id | doaj.art-6abd61c24c43485fae9188cefc117784 |
| institution | Directory Open Access Journal |
| issn | 1010-660X |
| language | English |
| last_indexed | 2024-03-12T08:32:54Z |
| publishDate | 2019-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Medicina |
| spelling | doaj.art-6abd61c24c43485fae9188cefc1177842023-09-02T17:28:49ZengMDPI AGMedicina1010-660X2019-06-0155629710.3390/medicina55060297medicina55060297Different Patterns of HIV-1 Replication in MACROPHAGES is Led by Co-Receptor UsageAna Borrajo0Alessandro Ranazzi1Michela Pollicita2Maria Concetta Bellocchi3Romina Salpini4Maria Vittoria Mauro5Francesca Ceccherini-Silberstein6Carlo Federico Perno7Valentina Svicher8Stefano Aquaro9Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, 00133 Roma, ItalyDepartment of Experimental Medicine and Surgery, University of Rome Tor Vergata, 00133 Roma, ItalyDepartment of Experimental Medicine and Surgery, University of Rome Tor Vergata, 00133 Roma, ItalyDepartment of Experimental Medicine and Surgery, University of Rome Tor Vergata, 00133 Roma, ItalyDepartment of Experimental Medicine and Surgery, University of Rome Tor Vergata, 00133 Roma, ItalyDepartment of Microbiology and Virology, Complex Operative Unit (UOC), Hospital of Cosenza, 87100 Cosenza, ItalyDepartment of Experimental Medicine and Surgery, University of Rome Tor Vergata, 00133 Roma, ItalyDepartment of Microbiology and Clinic Microbiology, University of Milan, 20162 Milan, ItalyDepartment of Experimental Medicine and Surgery, University of Rome Tor Vergata, 00133 Roma, ItalyDepartment of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy<i>Background and objectives:</i> 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. <i>Materials and Methods:</i> 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. <i>Results:</i> 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. <i>Conclusions:</i> 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.https://www.mdpi.com/1010-660X/55/6/297α chemokine receptor 4β-chemokine receptor 5human immunodeficiency virusmonocyte-derived macrophages |
| spellingShingle | Ana Borrajo Alessandro Ranazzi Michela Pollicita Maria Concetta Bellocchi Romina Salpini Maria Vittoria Mauro Francesca Ceccherini-Silberstein Carlo Federico Perno Valentina Svicher Stefano Aquaro Different Patterns of HIV-1 Replication in MACROPHAGES is Led by Co-Receptor Usage Medicina α chemokine receptor 4 β-chemokine receptor 5 human immunodeficiency virus monocyte-derived macrophages |
| title | Different Patterns of HIV-1 Replication in MACROPHAGES is Led by Co-Receptor Usage |
| title_full | Different Patterns of HIV-1 Replication in MACROPHAGES is Led by Co-Receptor Usage |
| title_fullStr | Different Patterns of HIV-1 Replication in MACROPHAGES is Led by Co-Receptor Usage |
| title_full_unstemmed | Different Patterns of HIV-1 Replication in MACROPHAGES is Led by Co-Receptor Usage |
| title_short | Different Patterns of HIV-1 Replication in MACROPHAGES is Led by Co-Receptor Usage |
| title_sort | different patterns of hiv 1 replication in macrophages is led by co receptor usage |
| topic | α chemokine receptor 4 β-chemokine receptor 5 human immunodeficiency virus monocyte-derived macrophages |
| url | https://www.mdpi.com/1010-660X/55/6/297 |
| work_keys_str_mv | AT anaborrajo differentpatternsofhiv1replicationinmacrophagesisledbycoreceptorusage AT alessandroranazzi differentpatternsofhiv1replicationinmacrophagesisledbycoreceptorusage AT michelapollicita differentpatternsofhiv1replicationinmacrophagesisledbycoreceptorusage AT mariaconcettabellocchi differentpatternsofhiv1replicationinmacrophagesisledbycoreceptorusage AT rominasalpini differentpatternsofhiv1replicationinmacrophagesisledbycoreceptorusage AT mariavittoriamauro differentpatternsofhiv1replicationinmacrophagesisledbycoreceptorusage AT francescaceccherinisilberstein differentpatternsofhiv1replicationinmacrophagesisledbycoreceptorusage AT carlofedericoperno differentpatternsofhiv1replicationinmacrophagesisledbycoreceptorusage AT valentinasvicher differentpatternsofhiv1replicationinmacrophagesisledbycoreceptorusage AT stefanoaquaro differentpatternsofhiv1replicationinmacrophagesisledbycoreceptorusage |