1. A simian-human immunodeficiency virus carrying the rt gene from Chinese CRF01_AE strain of HIV is sensitive to nucleoside reverse transcriptase inhibitors and has a highly genetic stability in vivo.
- Author
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Wang W, Yao N, Ju B, Dong Z, Cong Z, Jiang H, Qin C, and Wei Q
- Subjects
- Amino Acid Sequence, Animals, Anti-HIV Agents pharmacology, Cell Line, China, Cloning, Molecular, Disease Models, Animal, Drug Delivery Systems, HEK293 Cells, HIV physiology, HIV Infections blood, HIV Infections drug therapy, Humans, Leukocytes, Mononuclear drug effects, Macaca mulatta virology, Molecular Sequence Data, Plasmids genetics, RNA, Viral blood, Reassortant Viruses physiology, Reverse Transcriptase Inhibitors pharmacology, Simian Immunodeficiency Virus physiology, T-Lymphocytes cytology, T-Lymphocytes virology, Virus Replication, HIV genetics, HIV Reverse Transcriptase genetics, Reassortant Viruses genetics, Simian Immunodeficiency Virus genetics
- Abstract
Human immunodeficiency virus (HIV)-1 subtype CRF01_AE is one of the major HIV-1 subtypes that dominate the global epidemic. However, its drug resistance, associated mutations, and viral fitness have not been systemically studied, because available chimeric simian-HIVs (SHIVs) usually express the HIV-1 reverse transcriptase (rt) gene of subtype B HIV-1, which is different from subtype CRF01_AE HIV-1. In this study, a recombinant plasmid, pRT-SHIV/AE, was constructed to generate a chimeric RT-SHIV/AE by replacing the rt gene of simian immunodeficiency virus (SIVmac239) with the counterpart of Chinese HIV-1 subtype CRF01_AE. The infectivity, replication capacity, co-receptor tropism, drug sensitivity, and genetic stability of RT-SHIV/AE were characterized. The new chimeric RT-SHIV/AE effectively infected and replicated in human T cell line and rhesus peripheral blood mononuclear cells (rhPBMC). The rt gene of RT-SHIV/AE lacked the common mutation (T215I) associated with drug resistance. RT-SHIV-AE retained infectivity and immunogenicity, similar to that of its counterpart RT-SHIV/TC virus following intravenous inoculation in Chinese rhesus macaque. RT-SHIV-AE was more sensitive to nucleoside reverse transcriptase inhibitors (NRTIs) than the RT-SHIV/TC. RT-SHIV/AE was genetically stable in Chinese rhesus macaque. The new chimeric RT-SHIV/AE may be a valuable tool for evaluating the efficacy of the rt-based antiviral drugs against the subtype CRF01_AE HIV-1., (Copyright © 2014 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)
- Published
- 2014
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