High natural permissivity of primary rabbit cells for HIV-1, with a virion infectivity defect in macrophages as the final replication barrier
An immunocompetent, permissive, small-animal model would be valuable for the study of human immunodeficiency virus type 1 (HIV-1) pathogenesis and for the testing of drug and vaccine candidates. However, the development of such a model has been hampered by the inability of primary rodent cells to ef...
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| Main Authors: | , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
11. September 2010
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| In: |
Journal of virology
Year: 2010, Volume: 84, Issue: 23, Pages: 12300-12314 |
| ISSN: | 1098-5514 |
| DOI: | 10.1128/jvi.01607-10 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1128/jvi.01607-10 Verlag, lizenzpflichtig, Volltext: https://journals.asm.org/doi/10.1128/jvi.01607-10 
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| Author Notes: | Hanna-Mari Tervo and Oliver T. Keppler |
| Summary: | An immunocompetent, permissive, small-animal model would be valuable for the study of human immunodeficiency virus type 1 (HIV-1) pathogenesis and for the testing of drug and vaccine candidates. However, the development of such a model has been hampered by the inability of primary rodent cells to efficiently support several steps of the HIV-1 replication cycle. Although transgenesis of the HIV receptor complex and human cyclin T1 have been beneficial, additional late-phase blocks prevent robust replication of HIV-1 in rodents and limit the range of in vivo applications. In this study, we explored the HIV-1 susceptibility of rabbit primary T cells and macrophages. Envelope-specific and coreceptor-dependent entry of HIV-1 was achieved by expressing human CD4 and CCR5. A block of HIV-1 DNA synthesis, likely mediated by TRIM5, was overcome by limited changes to the HIV-1 gag gene. Unlike with mice and rats, primary cells from rabbits supported the functions of the regulatory viral proteins Tat and Rev, Gag processing, and the release of HIV-1 particles at levels comparable to those in human cells. While HIV-1 produced by rabbit T cells was highly infectious, a macrophage-specific infectivity defect became manifest by a complex pattern of mutations in the viral genome, only part of which were deamination dependent. These results demonstrate a considerable natural HIV-1 permissivity of the rabbit species and suggest that receptor complex transgenesis combined with modifications in gag and possibly vif of HIV-1 to evade species-specific restriction factors might render lagomorphs fully permissive to infection by this pathogenic human lentivirus. |
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| Item Description: | Gesehen am 03.11.2023 |
| Physical Description: | Online Resource |
| ISSN: | 1098-5514 |
| DOI: | 10.1128/jvi.01607-10 |