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.
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.
Key Laboratory of Human Diseases Comparative Medicine, Ministry of Health, Beijing 100021, PR China; Key Laboratory of Human Diseases Animal Models, State Administration of Traditional Chinese Medicine, Beijing 100021, PR China; Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences, No. 5 Panjiayuan Nanli, Chaoyang District, Beijing 100021, PR China; Comparative Medical Center, Peking Union Medical College, No. 5 Panjiayuan Nanli, Chaoyang District, Beijing 100021, PR China.
Wei
W
Wang
Comparative Medical Center, Peking Union Medical College, No. 5 Panjiayuan Nanli, Chaoyang District, Beijing 100021, PR China.
Nan
N
Yao
Comparative Medical Center, Peking Union Medical College, No. 5 Panjiayuan Nanli, Chaoyang District, Beijing 100021, PR China.
Bin
B
Ju
Comparative Medical Center, Peking Union Medical College, No. 5 Panjiayuan Nanli, Chaoyang District, Beijing 100021, PR China.
Zhihui
Z
Dong
Key Laboratory of Human Diseases Comparative Medicine, Ministry of Health, Beijing 100021, PR China; Key Laboratory of Human Diseases Animal Models, State Administration of Traditional Chinese Medicine, Beijing 100021, PR China; Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences, No. 5 Panjiayuan Nanli, Chaoyang District, Beijing 100021, PR China; Comparative Medical Center, Peking Union Medical College, No. 5 Panjiayuan Nanli, Chaoyang District, Beijing 100021, PR China.
Zhe
Z
Cong
Key Laboratory of Human Diseases Comparative Medicine, Ministry of Health, Beijing 100021, PR China; Key Laboratory of Human Diseases Animal Models, State Administration of Traditional Chinese Medicine, Beijing 100021, PR China; Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences, No. 5 Panjiayuan Nanli, Chaoyang District, Beijing 100021, PR China; Comparative Medical Center, Peking Union Medical College, No. 5 Panjiayuan Nanli, Chaoyang District, Beijing 100021, PR China.
Hong
H
Jiang
Key Laboratory of Human Diseases Comparative Medicine, Ministry of Health, Beijing 100021, PR China; Key Laboratory of Human Diseases Animal Models, State Administration of Traditional Chinese Medicine, Beijing 100021, PR China; Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences, No. 5 Panjiayuan Nanli, Chaoyang District, Beijing 100021, PR China; Comparative Medical Center, Peking Union Medical College, No. 5 Panjiayuan Nanli, Chaoyang District, Beijing 100021, PR China. Electronic address: qinchuan@pumc.edu.cn.
Chuan
C
Qin
Key Laboratory of Human Diseases Comparative Medicine, Ministry of Health, Beijing 100021, PR China; Key Laboratory of Human Diseases Animal Models, State Administration of Traditional Chinese Medicine, Beijing 100021, PR China; Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences, No. 5 Panjiayuan Nanli, Chaoyang District, Beijing 100021, PR China; Comparative Medical Center, Peking Union Medical College, No. 5 Panjiayuan Nanli, Chaoyang District, Beijing 100021, PR China. Electronic address: virolab@126.com.
Qiang
Q
Wei
D000595:Amino Acid Sequence; D000818:Animals; D019380:Anti-HIV Agents / Q000494:pharmacology; D002460:Cell Line; D002681:China; D003001:Cloning, Molecular; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D057809:HEK293 Cells; D006678:HIV / Q000235:genetics* / Q000502:physiology; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy; D054303:HIV Reverse Transcriptase / Q000235:genetics*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008253:Macaca mulatta / Q000821:virology; D008969:Molecular Sequence Data; D010957:Plasmids / Q000235:genetics; D012367:RNA, Viral / Q000097:blood; D016865:Reassortant Viruses / Q000235:genetics* / Q000502:physiology; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology; D015302:Simian Immunodeficiency Virus / Q000235:genetics* / Q000502:physiology; D013601:T-Lymphocytes / Q000166:cytology / Q000821:virology; D014779:Virus Replication
D019380:Anti-HIV Agents; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase
Antiretroviral therapy; CRF01_AE; HIV-1; Reverse transcriptase; Simian-human immunodeficiency virus