Parthasarathy Durgadevi, Pickthorn Stephanie, Ahmed Shamim, Mazurov Dmitry, Jeffy Jeffy, Shukla Rajni Kant, Sharma Amit, Herschhorn Alon
Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, MN, 55455, USA.
Department of Veterinary Biosciences, Department of Microbial Infection & Immunity, The Ohio State University, Columbus, OH, 43210, USA.
Npj Viruses. 2025 Jan 15;3(1):3. doi: 10.1038/s44298-024-00082-w.
HIV-1 envelope glycoproteins (Envs) mediate viral entry and are sole target of neutralizing antibodies. Thus, HIV-1 Envs must maintain a delicate balance between evading neutralizing antibodies while still preserving viral compatibility to mediate entry into target cells. Here, we studied the viral entry effeciency, fitness, and replication of an incompletely closed, transmitted/founder HIV-1 Envs (CH040), which are highly resistant to most bnAbs. CH040 Envs mediated HIV-1 entry to target cells as efficient as other primary Envs, suggesting that antibody resistance and efficient viral entry can develop independently. Expression of CH040 Envs was comparable to other Envs and most CH040 variants that were rationally engineered to increase bnAb resistance showed no significant decrease in their ability to mediate HIV-1 entry. We detected robust in vitro spread of SHIV CH040 in pig-tailed macaque lymphocytes that was comparable to efficient spread of other SHIVs. Our study provides insights into the relationship between bnAb resistance and efficient HIV-1 entry.
HIV-1包膜糖蛋白（Env）介导病毒进入，是中和抗体的唯一靶点。因此，HIV-1 Env必须在逃避中和抗体与保持病毒与靶细胞结合能力之间保持微妙平衡。在此，我们研究了一种不完全封闭的、传播/奠基型HIV-1 Env（CH040）的病毒进入效率、适应性和复制情况，该Env对大多数bnAb具有高度抗性。CH040 Env介导HIV-1进入靶细胞的效率与其他原始Env相当，这表明抗体抗性和高效的病毒进入可以独立发展。CH040 Env的表达与其他Env相当，大多数经过合理改造以增加bnAb抗性的CH040变体在介导HIV-1进入的能力上没有显著下降。我们检测到SHIV CH040在食蟹猴淋巴细胞中具有强劲的体外传播能力，与其他SHIV的高效传播相当。我们的研究为bnAb抗性与高效HIV-1进入之间的关系提供了见解。
