Authors:
Zainab H. Alwan
1
;
Gopal Reddy
2
and
Balasubramanyam Karanam
3
Affiliations:
1
Department of Community Health, Institute of Medical Technology, Middle Technical University Baghdad, Iraq
;
2
College of Veterinary Medicine, Tuskegee University, Tuskegee AL36088, U.S.A.
;
3
Department of Biology and Center for Cancer Research, Tuskegee University, Tuskegee, AL36088, U.S.A.
Keyword(s):
Kaiso, HIV-1, Transcriptional Factor, Zinc Finger, CD4, Viral Load.
Abstract:
The role of Kaiso, a POZ-ZF transcriptional factor in HIV infection, which has been disparagingly affecting African Natives as well as African Americans, has not been well studied. For these reasons, this research aimed to investigate the level of expression and the role of Kaiso in HIV-1 infected African Natives compared with patients in the United States. In silico data of 185 whole blood samples were analyzed to study gene expression by array in GEO (Gene expression Omnibus) dataset from the National Center for Biotechnology Information (NCBI). Different bioinformatics approaches were used to analyze the data. Two or more groups of samples were compared using GEO2R to identify differentially expressed genes across experimental conditions. Pathways that were significantly associated with specific gene sets were determined by Gene Set Enrichment analysis (GSEA). Results showed higher level of Kaiso expression in HIV-1 patients compared to healthy control (p = 3.89e-10), and it was s
ignificantly higher in African Natives compared to United States patients (p = 0.002). Importantly, this study revealed a negative correlation between Kaiso expression and CD4+ T cell count in HIV-1 infected African Native patients (p = 0.003). This negative correlation between Kaiso and CD4+ T cell count was accompanied by increased viral load in African Natives with a higher viral set point compared to US HIV-1 patients. These data may at least partly explain the reasons for faster progression to AIDS in African Natives than seen in US patients. Kaiso associated enrichment pathways showed that Kaiso upregulation may contribute to CD4 depletion in HIV-1 infection, and may upregulate HIV associated neurological impairment marker genes. The results also showed that Kaiso expression may also be associated with increased Wnt/β-catenin signaling pathway by downregulating GSK3β, MAPK1 and MAPK3 through different downregulated pathways in African Native patients. This study suggests that Kaiso may play a role in the crosstalk between different pathways in HIV-1 infection. In conclusion, the present study suggests, for the first time, that Kaiso expression levels may possibly play a role in the faster acceleration of HIV-1 infection towards AIDS in African ancestry patients and this may be through the involvement of Wnt/βcatenin signaling pathway. Data of this study also suggests that Kaiso expression level may contribute to increased crosstalk between different pathways in HIV-1 pathogenesis. Further studies are needed to fully delineate the role of Kaiso in different HIV1 infected ethnic groups through the involvement of different intermediary pathways.
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