Abstract
While human immunodeficiency virus type 1 and 2 (HIV-1 and HIV-2) share many similar traits, major differences in pathogenesis and clinical outcomes exist between the two viruses. The differential expression of host factors like microRNAs (miRNAs) in response to HIV-1 and HIV-2 infections are thought to influence the clinical outcomes presented by the two viruses. MicroRNAs are small non-coding RNA molecules which function in transcriptional and post-transcriptional regulation of gene expression. MiRNAs play a critical role in many key biological processes and could serve as putative biomarker(s) for infection. Identification of miRNAs that modulate viral life cycle, disease progression, and cellular responses to infection with HIV-1 and HIV-2 could reveal important insights into viral pathogenesis and provide new tools that could serve as prognostic markers and targets for therapeutic intervention. The aim of this study was to elucidate the differential expression profiles of host miRNAs in cells infected with HIV-1 and HIV-2 in order to identify potential differences in virus-host interactions between HIV-1 and HIV-2. Differential expression of host miRNA expression profiles was analyzed using the miRNA profiling polymerase chain reaction (PCR) arrays. Differentially expressed miRNAs were identified and their putative functional targets identified. The results indicate that hsa-miR 541-3p, hsa-miR 518f-3p, and hsa-miR 195-3p were consistently up-regulated only in HIV-1 infected cells. The expression of hsa-miR 1225-5p, hsa-miR 18a* and hsa-miR 335 were down modulated in HIV-1 and HIV-2 infected cells. Putative functional targets of these miRNAs include genes involved in signal transduction, metabolism, development and cell death.
Highlights
Human immunodeficiency virus type 1 and 2 (HIV-1 and HIV-2) are closely related retroviruses that share 30%–60% overall genetic homology and similar structural and genomic organization [1].In addition to structural similarities, these two related viruses exhibit functional similarities like cluster of differentiation 4 (CD4) binding, T-cell and mononuclear cell tropism, viral transmission, replication and pathogenesis [2,3,4]
Preliminary findings using peripheral blood mononuclear cells (PBMC) or Jurkat cells infected with HIV-1 or HIV-2 indicated that HIV-1 infection generated more reactive oxygen species (ROS), increased the expression of a larger number of molecules involved in cell signaling such as p47, p38α, c-Jun N-terminal kinases (JNK), c-Yes, total protein kinase C (PKC), and decreased the expression of molecules such as p38β, extracellular receptor kinases (ERK)1/2, X-linked inhibitor of apoptosis protein (XIAP) leading to increased cell death by apoptosis relative to HIV-2 infection
The expression profile of 352 host cellular miRNAs was assessed in PBMC isolated from three independent donors productively infected with HIV-1 (MN) or HIV-2 (ROD) (Table 1) to identify putative biomarkers of infection that could differentiate between the two viruses
Summary
Human immunodeficiency virus type 1 and 2 (HIV-1 and HIV-2) are closely related retroviruses that share 30%–60% overall genetic homology and similar structural and genomic organization [1].In addition to structural similarities, these two related viruses exhibit functional similarities like cluster of differentiation 4 (CD4) binding, T-cell and mononuclear cell tropism, viral transmission, replication and pathogenesis [2,3,4]. In spite of the similarities between HIV-1 and HIV-2, several studies have shown that the disease outcomes presented by these two viruses are distinct [5]. The exact mechanisms contributing to these distinct clinical outcomes in infections with the HIV-1 and HIV-2 viruses are not completely understood. One determinant of these differences may be a lower viral load observed in HIV-2 infected patients [10]. Studies have proposed that HIV-2 infection causes lower rates of T-cell activation and enhanced virus-specific immune responses leading to viral control in HIV-2 infections [11]. Preliminary findings using peripheral blood mononuclear cells (PBMC) or Jurkat cells infected with HIV-1 or HIV-2 indicated that HIV-1 infection generated more reactive oxygen species (ROS), increased the expression of a larger number of molecules involved in cell signaling such as p47, p38α, c-Jun N-terminal kinases (JNK), c-Yes, total protein kinase C (PKC), and decreased the expression of molecules such as p38β, extracellular receptor kinases (ERK)1/2, X-linked inhibitor of apoptosis protein (XIAP) leading to increased cell death by apoptosis relative to HIV-2 infection
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