Virology. 2015 Jan 15:475:37-45. doi: 10.1016/j.virol.2014.10.032

Infection of monkeys by simian-human immunodeficiency viruses with transmitted/founder clade C HIV-1 envelopes

用传递/始祖克隆C人类免疫缺陷病毒包膜感染猴子翻译改进

Mohammed Asmal¹, Corinne Luedemann¹, Christy L Lavine¹, Linh V Mach¹, Harikrishnan Balachandran¹, Christie Brinkley², Thomas N Denny², Mark G Lewis³, Hanne Anderson³, Ranajit Pal⁴, Devin Sok⁵, Khoa Le⁵, Matthias Pauthner⁵, Beatrice H Hahn⁶, George M Shaw⁶, Michael S Seaman¹, Norman L Letvin⁶, Dennis R Burton⁵, Joseph G Sodroski⁷, Barton F Haynes², Sampa Santra⁸

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¹ Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.

² Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.

³ BIOQUAL Inc., Rockville, MD 20852, USA.

⁴ Advanced BioScience Laboratories, Inc., Rockville, MD 20850, USA.

⁵ Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.

⁶ University of Pennsylvania, Department of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

⁷ Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.

⁸ Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. Electronic address: ssantra@bidmc.harvard.edu.

DOI: 10.1016/j.virol.2014.10.032 PMID: 25462344

摘要 Ai翻译

Simian-human immunodeficiency viruses (SHIVs) that mirror natural transmitted/founder (T/F) viruses in man are needed for evaluation of HIV-1 vaccine candidates in nonhuman primates. Currently available SHIVs contain HIV-1 env genes from chronically-infected individuals and do not reflect the characteristics of biologically relevant HIV-1 strains that mediate human transmission. We chose to develop clade C SHIVs, as clade C is the major infecting subtype of HIV-1 in the world. We constructed 10 clade C SHIVs expressing Env proteins from T/F viruses. Three of these ten clade C SHIVs (SHIV KB9 C3, SHIV KB9 C4 and SHIV KB9 C5) replicated in naïve rhesus monkeys. These three SHIVs are mucosally transmissible and are neutralized by sCD4 and several HIV-1 broadly neutralizing antibodies. However, like natural T/F viruses, they exhibit low Env reactivity and a Tier 2 neutralization sensitivity. Of note, none of the clade C T/F SHIVs elicited detectable autologous neutralizing antibodies in the infected monkeys, even though antibodies that neutralized a heterologous Tier 1 HIV-1 were generated. Challenge with these three new clade C SHIVs will provide biologically relevant tests for vaccine protection in rhesus macaques.

Keywords: HIV-1 Clade C; Mucosal transmission; SHIV; Transmitted/founder Env.

Keywords：infection of monkeys

关键词：猴人免疫缺陷病毒; 感染猴子

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Infection of monkeys by simian-human immunodeficiency viruses with transmitted/founder clade C HIV-1 envelopes

用传递/始祖克隆C人类免疫缺陷病毒包膜感染猴子 翻译改进

用传递/始祖克隆C人类免疫缺陷病毒包膜感染猴子翻译改进