Journal article
HIV-1 Adapts To Replicate in Cells Expressing Common Marmoset APOBEC3G and BST2
Journal of virology, Vol.90(2), pp.725-740
01/15/2016
DOI: 10.1128/JVI.02431-15
PMCID: PMC4702673
PMID: 26512082
Abstract
Previous studies have shown that a major block to HIV-1 replication in common marmosets operates at the level of viral entry and that this block can be overcome by adaptation of the virus in tissue-cultured cells. However, our current studies indicate that HIV-1 encounters additional postentry blocks in common marmoset peripheral blood mononuclear cells. Here, we show that the common marmoset APOBEC3G (A3G) and BST2 proteins block HIV-1 in cell cultures. Using a directed-evolution method that takes advantage of the natural ability of HIV-1 to mutate during replication, we have been able to overcome these blocks in tissue-cultured cells. In the adapted viruses, specific changes were observed in gag, vif, env, and nef. The contribution of these changes to virus replication in the presence of the A3G and BST2 restriction factors was studied. We found that certain amino acid changes in Vif and Env that arise during adaptation to marmoset A3G and BST2 allow the virus to replicate in the presence of these restriction factors. The changes in Vif reduce expression levels and encapsidation of marmoset APOBEC3G, while the changes in Env increase viral fitness and discretely favor cell-to-cell transmission of the virus, allowing viral escape from these restriction factors.
HIV-1 can infect only humans and chimpanzees. The main reason for this narrow tropism is the presence in many species of dominant-acting factors, known as restriction factors, that block viral replication in a species-specific way. We have been exploring the blocks to HIV-1 in common marmosets, with the ultimate goal of developing a new animal model of HIV-1 infection in these monkeys. In this study, we observed that common marmoset APOBEC3G and BST2, two known restriction factors, are able to block HIV-1 in cell cultures. We have adapted HIV-1 to replicate in the presence of these restriction factors and have characterized the mechanisms of escape. These studies can help in the development of a novel animal model for in vivo infection of marmosets with HIV-1-like viruses.
Details
- Title: Subtitle
- HIV-1 Adapts To Replicate in Cells Expressing Common Marmoset APOBEC3G and BST2
- Creators
- Alberto Fernández-Oliva - Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid, Madrid, SpainAndrés Finzi - Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, and Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USAHillel Haim - Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, and Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USALuis Menéndez-Arias - Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid, Madrid, SpainJoseph Sodroski - Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, and Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, USABeatriz Pacheco - Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid, Madrid, Spain Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, and Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA b.pacheco.phd@hotmail.com
- Resource Type
- Journal article
- Publication Details
- Journal of virology, Vol.90(2), pp.725-740
- DOI
- 10.1128/JVI.02431-15
- PMID
- 26512082
- PMCID
- PMC4702673
- ISSN
- 0022-538X
- eISSN
- 1098-5514
- Grant note
- AI63987 / NIAID NIH HHS P30AI060354 / NIAID NIH HHS P30 AI060354 / NIAID NIH HHS AI67854 / NIAID NIH HHS
- Language
- English
- Date published
- 01/15/2016
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984083883602771
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