Journal article
HIV-1 Mutation and recombination rates are different in Macrophages and T-cells
Viruses, Vol.8(4)
2016
Abstract
High rates of mutation and recombination help human immunodeficiency virus (HIV) to evade the immune system and develop resistance to antiretroviral therapy. Macrophages and T-cells are the natural target cells of HIV-1 infection. A consensus has not been reached as to whether HIV replication results in differential recombination between primary T-cells and macrophages. Here, we used HIV with silent mutation markers along with next generation sequencing to compare the mutation and the recombination rates of HIV directly in T lymphocytes and macrophages. We observed a more than four-fold higher recombination rate of HIV in macrophages compared to T-cells (p < 0.001) and demonstrated that this difference is not due to different reliance on C-X-C chemokine receptor type 4 (CXCR4) and C-C chemokine receptor type 5 (CCR5) co-receptors between T-cells and macrophages. We also found that the pattern of recombination across the HIV genome (hot and cold spots) remains constant between T-cells and macrophages despite a three-fold increase in the overall recombination rate. This indicates that the difference in rates is a general feature of HIV DNA synthesis during macrophage infection. In contrast to HIV recombination, we found that T-cells have a 30% higher mutation rate than macrophages (p < 0.001) and that the mutational profile is similar between these cell types. Unexpectedly, we found no association between mutation and recombination in macrophages, in contrast to T-cells. Our data highlights some of the fundamental difference of HIV recombination and mutation amongst these two major target cells of infection. Understanding these differences will provide invaluable insights toward HIV evolution and how the virus evades immune surveillance and anti-retroviral therapeutics.
Details
- Title
- HIV-1 Mutation and recombination rates are different in Macrophages and T-cells
- Authors/Creators
- D. Cromer (Author/Creator) - Kirby InstituteT. Schlub (Author/Creator) - The University of SydneyR. Smyth (Author/Creator) - Burnet InstituteA. Grimm (Author/Creator) - Kirby InstituteA. Chopra (Author/Creator) - Murdoch UniversityS. Mallal (Author/Creator) - Murdoch UniversityM. Davenport (Author/Creator) - UNSW SydneyJ. Mak (Author/Creator) - Biosecurity Flagship, CSIRO (AAHL), Geelong VIC 3220, Australia.
- Publication Details
- Viruses, Vol.8(4)
- Publisher
- MDPI
- Identifiers
- 991005540440307891
- Copyright
- © 2016 by the authors
- Murdoch Affiliation
- Institute for Immunology and Infectious Diseases
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.66 HIV
- 1.66.46 HIV Pathogenesis
- Web Of Science research areas
- Virology
- ESI research areas
- Microbiology