ABSTRACT
There is limited data on the role of asymptomatic STIs (aSTIs) on the risk of human immunodeficiency virus (HIV) acquisition in the male genital tract (MGT). The impact of foreskin removal on lowering HIV acquisition is well described, but molecular events leading to HIV acquisition are unclear. Here, in this pilot study, we show that asymptomatic urethral infection with Chlamydia trachomatis (CT) significantly impacts the foreskin proteome composition. We developed and optimized a shotgun liquid chromatography coupled tandem mass spectrometry (MS)-based proteomics approach and utilized this on foreskins collected at medical male circumcision (MMC) from 16 aSTI+ men and 10 age-matched STI- controls. We used a novel bioinformatic metaproteomic pipeline to detect differentially expressed (DE) proteins. Gene enrichment ontology analysis revealed proteins associated with inflammatory and immune activation function in both inner and outer foreskin from men with an aSTI. Neutrophil activation/degranulation and viral-evasion proteins were significantly enriched in foreskins from men with aSTI, whereas homotypic cell-cell adhesion proteins were enriched in foreskin tissue from men without an aSTI. Collectively, our data show that asymptomatic urethral sexually transmitted infections result in profound alterations in epithelial tissue that are associated with depletion of barrier integrity and immune activation.
ABSTRACT
In addition to immunological disorders, human immunodeficiency virus (HIV) also causes metabolic abnormalities. Though successful in viral suppression and immune restoration, continued use of antiretroviral therapy (ART) has also been linked to the development of several metabolic ailments. Currently, the only clinical markers used to manage and monitor the development of HIV-induced metabolic disorders, disease progression as well as observing individual's response to antiviral treatment are CD4 count, viral loads and several other single variable colometric assays. Despite the common use of these clinical markers, these markers remain unreliable and limited in the ability to monitor the development of metabolic disorders as well as monitor treatment response. Given these limitations, it is imperative to discover and develop reliable biological markers for overall HIV disease management. Here, Raman spectroscopy was used to profile metabolic changes in the plasma of 22 HIV+ receiving a first-line tenofovir-based combination antiretroviral therapy compared to their 8 HIV+ ART- and 10 HIV- counterparts. Multivariate statistical analysis was performed in order to classify the samples into their respective groups and to identify significantly altered metabolites between the control and experimental groups. Orthogonal Projections to Latent Structures Discriminant Analysis (OPLS-DA) discriminant analysis identified significant differences (p < 0.05) in 9 different metabolites. Alterations were identified in spectral regions associated with glucose (1124 cm-1), lipids/phospholipids (1116 cm-1, 1098 cm-1, 1077 cm-1), proteins (1120 cm-1), nucleic acids (1081 cm-1) and phenylalanine (1103 cm-1). Pathway analysis also revealed 3 significantly altered pathways. This study presented the reproducible nature of Raman spectroscopy in distinguishing between HIV-infected (treated and untreated) and uninfected blood plasma and allowed for the detection and identification of treatment induced metabolite changes. The results obtained in the study may, therefore, give insights into understanding the metabolic effect of HIV therapy.
