Coexpression Network Analysis of Benign and Malignant Phenotypes of SIV-Infected Sooty Mangabey and Rhesus MacaqueReportar como inadecuado

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Journal Title:



Volume 11, Number 6


Public Library of Science | 2016-06-09, Pages e0156170-e0156170

Type of Work:

Article | Final Publisher PDF

Abstract: To explore the differences between the extreme SIV infection phenotypes, nonprogression BEN: benign to AIDS in sooty mangabeys SMs and progression to AIDS MAL: malignant in rhesus macaques RMs, we performed an integrated dual positive-negative connectivity DPNC analysis of gene coexpression networks GCN based on publicly available big data sets in the GEO database of NCBI. The microarray-based gene expression data sets were generated, respectively, from the peripheral blood of SMs and RMs at several time points of SIV infection. Significant differences of GCN changes in DPNC values were observed in SIV-infected SMs and RMs. There are three groups of enriched genes or pathways EGPs that are associated with three SIV infection phenotypes BEN+, MAL+ and mixed BEN+-MAL+. The MAL+ phenotype in SIV-infected RMs is specifically associated with eight EGPs, including the protein ubiquitin proteasome system, p53, granzyme A, gramzyme B, polo-like kinase, Glucocorticoid receptor, oxidative phosyphorylation and mitochondrial signaling. Mitochondrial endosymbiotic dysfunction is solely present in RMs. Specific BEN+ pattern changes in four EGPs are identified in SIV-infected SMs, including the pathways contributing to interferon signaling, BRCA1-DNA damage response, PKR-INF induction and LGALS8. There are three enriched pathways PRR-activated IRF signaling, RIG1-like receptor and PRR pathway contributing to the mixed BEN+-MAL+ phenotypes of SIV infections in RMs and SMs, suggesting that these pathways play a dual role in the host defense against viral infections. Further analysis of Hub genes in these GCNs revealed that the genes LGALS8 and IL-17RA, which positively regulate the barrier function of the gut mucosa and the immune homeostasis with the gut microbiota exosymbiosis, were significantly differentially expressed in RMs and SMs. Our data suggest that there exists an exo- dysbiosis of the gut microbiota and endo- mitochondrial dysfunction symbiotic imbalance EESI in HIV-SIV infections. Dissecting the mechanisms of the exo-endo symbiotic balance EESB that maintains immune homeostasis and the EESI problems in HIV-SIV infections may lead to a better understanding of the pathogenesis of AIDS and the development of novel interventions for the rational control of this disease.

Subjects: Biology, Genetics - Biology, Virology - Health Sciences, Pathology - Research Funding: This work was funded by grants from the Bill and Melinda Gates Foundation through the Grant Challenges Explorations Initiative S.H.H., NIH R37-AI66998-P30-AI-504 to G.S., and RR000165-OD011132 to the Yerkes National Primate Research Center and the Emory Center for AIDS Research, National Natural Science Foundation of China 30971642Y.H.Z. and Natural Science Foundation of Hubei Province of China 2009CDA161Y.H.Z

Keywords: Science and Technology - Multidisciplinary Sciences - NEUROCOGNITIVE DISORDERS - IMMUNE ACTIVATION - NATURAL HOSTS - IN-VITRO - IMMUNODEFICIENCY - CELLS - GENE - APOPTOSIS - EXPRESSION - SIV - Gene expression - Rhesus monkeys - AIDS - Mitochondria - Pathogenesis - Opportunistic infections - Genetic networks -

Autor: Zhao-Wan Yang, Yan-Hua Jiang, Chuang Ma, Guido Silvestri, Steven Bosinger, Bai-Lian Li, Ambrose Jong, Yan-Hong Zhou, Sheng-He Hua



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