Coexpression Network Analysis of Benign and Malignant Phenotypes of SIV-Infected Sooty Mangabey and Rhesus Macaque.
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.
Hubei Bioinformatics and Molecular Imaging Key Laboratory, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.
Zhao-Wan
ZW
Yang
Hubei Bioinformatics and Molecular Imaging Key Laboratory, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.
Yan-Hua
YH
Jiang
Saban Research Institute of Children's Hospital Los Angeles, Department of Pediatrics, University of Southern California, Los Angeles, California, United States of America.
Chuang
C
Ma
Yerkes National Primate Research Center, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, United States of America.
Guido
G
Silvestri
Yerkes National Primate Research Center, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, United States of America.
Steven E
SE
Bosinger
Ecological Complexity and Modeling Laboratory, University of California Riverside, Riverside, CA 92521-0124, United States of America.
Bai-Lian
BL
Li
Saban Research Institute of Children's Hospital Los Angeles, Department of Pediatrics, University of Southern California, Los Angeles, California, United States of America.
Ambrose
A
Jong
Hubei Bioinformatics and Molecular Imaging Key Laboratory, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.
Yan-Hong
YH
Zhou
Hubei Bioinformatics and Molecular Imaging Key Laboratory, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.|Saban Research Institute of Children's Hospital Los Angeles, Department of Pediatrics, University of Southern California, Los Angeles, California, United States of America.
Sheng-He
SH
Huang
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D016665:Cercocebus atys / Q000235:genetics* / Q000276:immunology / Q000821:virology; D053263:Gene Regulatory Networks; D007113:Immunity, Innate / Q000235:genetics / Q000276:immunology; D008253:Macaca mulatta / Q000235:genetics* / Q000276:immunology / Q000821:virology; D020411:Oligonucleotide Array Sequence Analysis; D015398:Signal Transduction; D016097:Simian Acquired Immunodeficiency Syndrome / Q000235:genetics* / Q000276:immunology / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000302:isolation & purification*; D013045:Species Specificity