Glycan dependent phenotype differences of HIV-1 generated from macrophage versus CD4+ T helper cell populations
Human immunodeficiency virus type 1 (HIV-1) is able to infect a variety of cell types with differences in entry efficiency and replication kinetics determined by the host cell type or the viral phenotype. The phenotype of the virus produced from these various cell types, including infectivity, co-re...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-06-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1107349/full |
| _version_ | 1797798527491899392 |
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| author | Edwin J. Heeregrave Jordan Thomas Toni M. van Capel Esther C. de Jong Georgios Pollakis William A. Paxton William A. Paxton |
| author_facet | Edwin J. Heeregrave Jordan Thomas Toni M. van Capel Esther C. de Jong Georgios Pollakis William A. Paxton William A. Paxton |
| author_sort | Edwin J. Heeregrave |
| collection | DOAJ |
| description | Human immunodeficiency virus type 1 (HIV-1) is able to infect a variety of cell types with differences in entry efficiency and replication kinetics determined by the host cell type or the viral phenotype. The phenotype of the virus produced from these various cell types, including infectivity, co-receptor usage and neutralisation sensitivity, may also be affected by the characteristics of the producing cell. This can be due to incorporation of variant cell-specific molecules or differences in post-translational modifications of the gp41/120 envelope. In this study we produced genetically identical virus strains from macrophages, CD4-enriched lymphocytes as well as Th1 and Th2 CD4+ cell lines and compared each different virus stock for their infectivity in various cell types and sensitivity to neutralisation. In order to study the effect of the producer host cell on the virus phenotype, virus stocks were normalised on infectivity and were sequenced to confirm env gene homogeneity. Virus production by Th1 or Th2 cells did not compromise infectivity of the variant cell types tested. We observed no difference in sensitivity to co-receptor blocking agents upon viral passage through Th1 and Th2 CD4+ cell lineages nor did this affect DC-SIGN-mediated viral capture as measured in a transfer assay to CD4+ lymphocytes. Virus produced by macrophages was comparably sensitive to CC-chemokine inhibition as was virus generated from the array of CD4+ lymphocytes. We identified that virus produced from macrophages was fourteen times more resistant to 2G12 neutralisation than virus produced from CD4+ lymphocytes. Macrophage-produced dual-tropic (R5/X4) virus was six times more efficiently transmitted to CD4+ cells than lymphocyte-derived HIV-1 (p<0.0001) after DCSIGN capture. These results provide further insights to what extent the host cell influences viral phenotype and thereby various aspects of HIV-1 pathogenesis but suggest that viruses generated from Th1 versus Th2 cells are consistent in phenotype. |
| first_indexed | 2024-03-13T04:05:05Z |
| format | Article |
| id | doaj.art-3fd53d6cc69a497f91daec1c192d0ab8 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-13T04:05:05Z |
| publishDate | 2023-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-3fd53d6cc69a497f91daec1c192d0ab82023-06-21T07:58:16ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-06-011410.3389/fimmu.2023.11073491107349Glycan dependent phenotype differences of HIV-1 generated from macrophage versus CD4+ T helper cell populationsEdwin J. Heeregrave0Jordan Thomas1Toni M. van Capel2Esther C. de Jong3Georgios Pollakis4William A. Paxton5William A. Paxton6Laboratory of Experimental Virology, Department of Medical Microbiology, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, NetherlandsDepartment of Clinical Infection, Microbiology and Immunology, Institute of Veterinary and Ecological Sciences, University of Liverpool, Liverpool, United KingdomDepartment of Experimental Immunology, University Medical Center, University of Amsterdam, Amsterdam, NetherlandsDepartment of Experimental Immunology, University Medical Center, University of Amsterdam, Amsterdam, NetherlandsDepartment of Experimental Immunology, University Medical Center, University of Amsterdam, Amsterdam, NetherlandsLaboratory of Experimental Virology, Department of Medical Microbiology, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, NetherlandsDepartment of Clinical Infection, Microbiology and Immunology, Institute of Veterinary and Ecological Sciences, University of Liverpool, Liverpool, United KingdomHuman immunodeficiency virus type 1 (HIV-1) is able to infect a variety of cell types with differences in entry efficiency and replication kinetics determined by the host cell type or the viral phenotype. The phenotype of the virus produced from these various cell types, including infectivity, co-receptor usage and neutralisation sensitivity, may also be affected by the characteristics of the producing cell. This can be due to incorporation of variant cell-specific molecules or differences in post-translational modifications of the gp41/120 envelope. In this study we produced genetically identical virus strains from macrophages, CD4-enriched lymphocytes as well as Th1 and Th2 CD4+ cell lines and compared each different virus stock for their infectivity in various cell types and sensitivity to neutralisation. In order to study the effect of the producer host cell on the virus phenotype, virus stocks were normalised on infectivity and were sequenced to confirm env gene homogeneity. Virus production by Th1 or Th2 cells did not compromise infectivity of the variant cell types tested. We observed no difference in sensitivity to co-receptor blocking agents upon viral passage through Th1 and Th2 CD4+ cell lineages nor did this affect DC-SIGN-mediated viral capture as measured in a transfer assay to CD4+ lymphocytes. Virus produced by macrophages was comparably sensitive to CC-chemokine inhibition as was virus generated from the array of CD4+ lymphocytes. We identified that virus produced from macrophages was fourteen times more resistant to 2G12 neutralisation than virus produced from CD4+ lymphocytes. Macrophage-produced dual-tropic (R5/X4) virus was six times more efficiently transmitted to CD4+ cells than lymphocyte-derived HIV-1 (p<0.0001) after DCSIGN capture. These results provide further insights to what extent the host cell influences viral phenotype and thereby various aspects of HIV-1 pathogenesis but suggest that viruses generated from Th1 versus Th2 cells are consistent in phenotype.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1107349/fullHIV-1macrophagesT helperglycanphenotypes |
| spellingShingle | Edwin J. Heeregrave Jordan Thomas Toni M. van Capel Esther C. de Jong Georgios Pollakis William A. Paxton William A. Paxton Glycan dependent phenotype differences of HIV-1 generated from macrophage versus CD4+ T helper cell populations Frontiers in Immunology HIV-1 macrophages T helper glycan phenotypes |
| title | Glycan dependent phenotype differences of HIV-1 generated from macrophage versus CD4+ T helper cell populations |
| title_full | Glycan dependent phenotype differences of HIV-1 generated from macrophage versus CD4+ T helper cell populations |
| title_fullStr | Glycan dependent phenotype differences of HIV-1 generated from macrophage versus CD4+ T helper cell populations |
| title_full_unstemmed | Glycan dependent phenotype differences of HIV-1 generated from macrophage versus CD4+ T helper cell populations |
| title_short | Glycan dependent phenotype differences of HIV-1 generated from macrophage versus CD4+ T helper cell populations |
| title_sort | glycan dependent phenotype differences of hiv 1 generated from macrophage versus cd4 t helper cell populations |
| topic | HIV-1 macrophages T helper glycan phenotypes |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1107349/full |
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