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Cataloguing of Potential HIV Susceptibility Factors during the Menstrual Cycle of Pigtail Macaques

ABSTRACT: Our earlier studies in pig-tailed macaques demonstrated varying SHIV susceptibility during the menstrual cycle, likely caused by cyclic variations in immune responses in the female genital tract. There is concern that high-dose, long-lasting, injectable progestin-based contraception could mimic the luteal phase and predispose women to HIV-1 acquisition and transmission. In this study, we adopted a systems biology approach employing proteomics (tandem mass spectrometry), transcriptomics (RNA microarray hybridization), and other specific protein assays (enzyme-linked immunosorbent assays and multiplex chemokine-cytokine measurements) to characterize the effects of hormonal changes on the expression of innate factors and secreted proteins in the macaque vagina. Several antiviral factors and pathways (including acute phase response signaling and complement system) were overexpressed in the follicular phase. Conversely, during the luteal phase there were factors overexpressed (including moesins, syndecans, integrins, among others) that could play direct or indirect roles in enhancing HIV-1 infection. Thus, our study showed that specific pathways and proteins/genes might be working in tandem to regulate innate immunity, thus fostering further investigation and future design of approaches to help counter HIV-1 acquisition in the female genital tract.

ORGANISM(S): Macaca nemestrina Macaca mulatta

PROVIDER: GSE68079 | GEO | 2015/07/08

SECONDARY ACCESSION(S): PRJNA281705

REPOSITORIES: GEO

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Project description:HIV-infected persons are at increased risk for developing pulmonary diseases including chronic obstructive pulmonary disease (COPD), and the fungal opportunistic pathogen, Pneumocystis jirovecii (Pc) has been implicated in the pathogenesis of HIV-related COPD. We previously developed a non-human primate model of HIV-related COPD using simian-human immunodeficiency virus (SHIV) and Pc co-infection in cynomolgus macaques. In the present study we examined gene expression profiles in lung tissue from SHIV/Pc co-infected monkeys with COPD and compared them to SHIV-infected monkeys infected with normal lung function. Microarray technology was used to develop gene profiles, and differential gene expression was determined by a comparative evaluation of competing normalization methods applied to our expression data set followed by validation using quantitative real-time polymerase chain reaction analysis for select genes. Of over 52,000 transcripts representing more than 20,000 genes analyzed, the SHIV/Pc infected macaques with COPD exhibited 243 differentially expressed (DE) genes compared to SHIV-infected monkeys with normal lung function. DE genes fell into a number of functional categories which may be important in COPD development including: inflammation (pulmonary surfactants A2, B, C, D, upregulated; alternative macrophage activation-associated CC chemokine, upregulated), protease/antiprotease balance (cathepsin H, upregulated; alpha-1-chymotrypsin and secretory leukocyte peptidase inhibitor, downregulated), redox balance (glutathione peroxidase 4 and mitochondrial aldehyde dehydrogenase 2, upregulated) and tissue homeostasis (connective tissue growth factor, downregulated; ornithine decarboxylase antizyme, upregulated). These results identify factors and pathways that may be involved in early development of Pneumocystis and SHIV-associated COPD and reveal several novel, potential therapeutic targets. There are totally 11 samples in the experiment. The sample breakdown is as follows: KN14(group 1) is a true control in that the monkey was not infected with simian-human immunodeficiency virus (SHIV) nor was it colonized with Pneumocystis. KN02, KN03, KN07 and KN08 (group 2) are also controls of a sort. They were infected with SHIV but they did not become colonized with Pneumocystis. The remainder (KN01, KN04, KN06, KN11, KN12, KN13) (group3) were both infected with SHIV and colonized with Pneumocystis. The primary interest is in comparing the two SHIV-infected groups (2 and 3)

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Cataloguing of Potential HIV Susceptibility Factors during the Menstrual Cycle of Pigtail Macaques

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