Academic Journal
Rational design and in vivo selection of SHIVs encoding transmitted/founder subtype C HIV-1 envelopes.
| العنوان: | Rational design and in vivo selection of SHIVs encoding transmitted/founder subtype C HIV-1 envelopes. |
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| المؤلفون: | Sean P O'Brien, Adrienne E Swanstrom, Amarendra Pegu, Sung-Youl Ko, Taina T Immonen, Gregory Q Del Prete, Christine M Fennessey, Jason Gorman, Kathryn E Foulds, Stephen D Schmidt, Nicole Doria-Rose, Carolyn Williamson, Theodora Hatziioannou, Paul D Bieniasz, Hui Li, George M Shaw, John R Mascola, Richard A Koup, Peter D Kwong, Jeffrey D Lifson, Mario Roederer, Brandon F Keele |
| المصدر: | PLoS Pathogens, Vol 15, Iss 4, p e1007632 (2019) |
| بيانات النشر: | Public Library of Science (PLoS) |
| سنة النشر: | 2019 |
| المجموعة: | Directory of Open Access Journals: DOAJ Articles |
| مصطلحات موضوعية: | Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5 |
| الوصف: | Chimeric Simian-Human Immunodeficiency Viruses (SHIVs) are an important tool for evaluating anti-HIV Env interventions in nonhuman primate (NHP) models. However, most unadapted SHIVs do not replicate well in vivo limiting their utility. Furthermore, adaptation in vivo often negatively impacts fundamental properties of the Env, including neutralization profiles. Transmitted/founder (T/F) viruses are particularly important to study since they represent viruses that initiated primary HIV-1 infections and may have unique attributes. Here we combined in vivo competition and rational design to develop novel subtype C SHIVs containing T/F envelopes. We successfully generated 19 new, infectious subtype C SHIVs, which were tested in multiple combinatorial pools in Indian-origin rhesus macaques. Infected animals attained peak viremia within 5 weeks ranging from 103 to 107 vRNA copies/mL. Sequence analysis during primary infection revealed 7 different SHIVs replicating in 8 productively infected animals with certain clones prominent in each animal. We then generated 5 variants each of 6 SHIV clones (3 that predominated and 3 undetectable after pooled in vivo inoculations), converting a serine at Env375 to methionine, tyrosine, histidine, tryptophan or phenylalanine. Overall, most Env375 mutants replicated better in vitro and in vivo than wild type with both higher and earlier peak viremia. In 4 of these SHIV clones (with and without Env375 mutations) we also created mutations at position 281 to include serine, alanine, valine, or threonine. Some Env281 mutations imparted in vitro replication dynamics similar to mutations at 375; however, clones with both mutations did not exhibit incremental benefit. Therefore, we identified unique subtype C T/F SHIVs that replicate in rhesus macaques with improved acute phase replication kinetics without altering phenotype. In vivo competition and rational design can produce functional SHIVs with globally relevant HIV-1 Envs to add to the growing number of SHIV clones for HIV-1 research ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1553-7366 1553-7374 |
| Relation: | https://doi.org/10.1371/journal.ppat.1007632; https://doaj.org/toc/1553-7366; https://doaj.org/toc/1553-7374; https://doaj.org/article/223d0101fda54e459f18cac090f5311b |
| DOI: | 10.1371/journal.ppat.1007632 |
| الاتاحة: | https://doi.org/10.1371/journal.ppat.1007632 https://doaj.org/article/223d0101fda54e459f18cac090f5311b |
| رقم الانضمام: | edsbas.7AEEF825 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 15537366 15537374 |
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| DOI: | 10.1371/journal.ppat.1007632 |