HIV-1 Adapts To Replicate in Cells Expressing Common Marmoset APOBEC3G and BST2
| Autor: | Andrés Finzi, Hillel Haim, Joseph Sodroski, Beatriz Pacheco, Alberto Fernández-Oliva, Luis Menéndez-Arias |
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| Přispěvatelé: | Fundación Ramón Areces, Ministerio de Economía y Competitividad (España) |
| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Virus Cultivation viruses Immunology Human Immunodeficiency Virus Proteins Human immunodeficiency virus (HIV) Adaptation Biological medicine.disease_cause Virus Replication Microbiology Cell Line 03 medical and health sciences Antigens CD Virology biology.animal Cytidine Deaminase medicine Animals Humans biology Extramural Marmoset virus diseases Amino acid substitution Callithrix ANTIGENS CD Virus-Cell Interactions 030104 developmental biology Amino Acid Substitution Insect Science Mutation HIV-1 Christian ministry |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname |
| ISSN: | 1098-5514 2013-4878 |
| Popis: | 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 Spanish Ministry of Economy and Competitiveness grant (BIO2013-48788-C2-1-R) to L.M.-A.; and by an institutional grant from the Fundación Ramón Areces to the Centro de Biología Molecular Severo Ochoa |
| Databáze: | OpenAIRE |
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