Early Emergence and Selection of a SIV-LTR C/EBP Site Variant in SIV-Infected Macaques That Increases Virus Infectivity
| العنوان: | Early Emergence and Selection of a SIV-LTR C/EBP Site Variant in SIV-Infected Macaques That Increases Virus Infectivity |
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| المؤلفون: | Janice E. Clements, Elizabeth L. Engle, Lucio Gama, Shruthi Ravimohan, M. Christine Zink |
| المصدر: | PLoS ONE PLoS ONE, Vol 7, Iss 8, p e42801 (2012) |
| بيانات النشر: | Public Library of Science, 2012. |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | Time Factors, viruses, Simian Acquired Immunodeficiency Syndrome, lcsh:Medicine, medicine.disease_cause, Virus Replication, 0302 clinical medicine, Enhancer binding, lcsh:Science, Immune Response, In Situ Hybridization, Infectivity, 0303 health sciences, Multidisciplinary, Ccaat-enhancer-binding proteins, Brain, Animal Models, Long terminal repeat, 3. Good health, medicine.anatomical_structure, Disease Progression, Medicine, Infectious diseases, Simian Immunodeficiency Virus, Macaque, Research Article, Evolutionary Processes, Genotype, Immunology, Retrovirology and HIV immunopathogenesis, Spleen, Emergence, Viral diseases, Biology, Microbiology, Virus, 03 medical and health sciences, Model Organisms, Virology, medicine, Animals, Humans, Adaptation, 030304 developmental biology, Evolutionary Biology, Interleukin-6, Macrophages, lcsh:R, Terminal Repeat Sequences, HIV, Genetic Variation, Interferon-beta, Simian immunodeficiency virus, HEK293 Cells, Viral replication, Mutation, CCAAT-Enhancer-Binding Proteins, Macaca, lcsh:Q, 030217 neurology & neurosurgery, Viral Transmission and Infection, Coevolution |
| الوصف: | CCAAT/enhancer binding protein (C/EBP)b, and C/EBP binding sites in the HIV/SIV- long terminal repeat (LTR) are crucial for regulating transcription and for IFNb-mediated suppression of virus replication in macrophages, the predominant source of productive virus replication in the brain. We investigated sequence variation within the SIV-LTR C/EBP sites that may be under selective pressure in vivo and therefore associated with disease progression. Using the SIV-macaque model, we examined viral LTR sequences derived from the spleen, a site of macrophage and lymphocyte infection, and the brain from macaques euthanized at 10, 21, 42, 48 and 84 days postinoculation (p.i.). A dominant variant, DS1C/A, containing an adenine-to-guanine substitution and a linked cytosine-to-adenine substitution in the downstream (DS1) C/EBP site, was detected in the spleen at 10 days p.i. The DS1C/A genotype was not detected in the brain until 42 days p.i., after which it was the predominant replicating genotype in both brain and spleen. Functional characterization of the DS1C/A containing SIV showed increased infectivity with or without IFNb treatment over the wild-type virus, SIV/17E-Fr. The DS1C/A C/EBP site had higher affinity for both protein isoforms of C/EBPb compared to the wild-type DS1 C/EBP site. Cytokine expression in spleen compared to brain implicated IFNb and IL-6 responses as part of the selective pressures contributing to emergence of the DS1C/A genotype in vivo. These studies demonstrate selective replication of virus containing the DS1C/A genotype that either emerges very early in spleen and spreads to the brain, or evolves independently in the brain when IFNb and IL-6 levels are similar to that found in spleen earlier in infection. |
| اللغة: | English |
| تدمد: | 1932-6203 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b32db0ff11934f17016deb7b5183fc3cTest http://europepmc.org/articles/PMC3428313Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....b32db0ff11934f17016deb7b5183fc3c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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