Characterization of a Neutralization-Escape Variant of SHIV_KU-1, a Virus That Causes Acquired Immune Deficiency Syndrome in Pig-Tailed Macaques

详细信息    查看全文

• 作者：Narayan ; Shanil V. ; Mukherjee ; Sampa ; Jia ; Fenglan ; Li ; Zhuang ; Wang ; Chunyang ; Foresman ; Larry ; et. al.
• 刊名：Virology
• 出版年：1999
• 出版时间：March 30, 1999
• 年：1999
• 卷：256
• 期：1
• 页码：54-63
• 全文大小：149 K

文摘

A chimeric simian-human immunodeficiency virus (SHIV-4) containing thetat, rev, vpu,andenvgenes of HIV type 1 (HIV-1) in a genetic background of SIV_mac239 was used to develop an animal model in which a primate lentivirus expressing the HIV-1 envelope glycoprotein caused acquired immune deficiency syndrome (AIDS) in macaques. An SHIV-infected pig-tailed macaque that died from AIDS at 24 weeks postinoculation experienced two waves of viremia: one extending from weeks 2–8 and the second extending from week 18 until death. Virus (SHIV_KU-1) isolated during the first wave was neutralized by antibodies appearing at the end of the first viremic phase, but the virus (SHIV_KU-1b) isolated during the second viremic phase was not neutralized by these antibodies. Inoculation of SHIV_KU-1binto 4 pig-tailed macaques resulted in severe CD4⁺T cell loss by 2 weeks postinoculation, and all 4 macaques died from AIDS at 23–34 weeks postinoculation. Because this virus had a neutralization-resistant phenotype, we sequenced theenvgene and compared these sequences with those of theenvgene of SHIV_KU-1and parental SHIV-4. With reference to SHIV-4, SHIV_KU-1bhad 18 and 6 consensus amino acid substitutions in the gp120 and gp41 regions of Env, respectively. These compared with 10 and 3 amino acid substitutions in the gp120 and gp41 regions of SHIV_KU-1. Our data suggested that SHIV_KU-1and SHIV_KU-1bprobably evolved from a common ancestor but that SHIV_KU-1bdid not evolve from SHIV_KU-1. A chimeric virus, SHIV_KU-1bMC17, constructed with the consensusenvfrom the SHIV_KU-1bon a background of SHIV-4, confirmed that amino acid substitutions in Env were responsible for the neutralization-resistant phenotype. These results are consistent with the hypothesis that neutralizing antibodies induced by SHIV_KU-1in pig-tailed macaque resulted in the selection of a neutralization-resistant virus that was responsible for the second wave of viremia.