Comparison of miRNA Expression Profiles between HIV-1 and HIV-2 Infected Monocyte-Derived Macrophages (MDMs) and Peripheral Blood Mononuclear Cells (PBMCs).

Santanu Biswas,Indira Hewlett,Mohan Haleyurgirisetty,Krishnakumar Devadas,Emily Chen,Sherwin Lee

doi:10.3390/ijms21186970

Abstract

During the progression of HIV-1 infection, macrophage tropic HIV-1 that use the CCR5 co-receptor undergoes a change in co-receptor use to CXCR4 that is predominately T cell tropic. This change in co-receptor preference makes the virus able to infect T cells. HIV-2 is known to infect MDMs and T cells and is dual tropic. The aim of this study was to elucidate the differential expression profiles of host miRNAs and their role in cells infected with HIV-1/HIV-2. To achieve this goal, a comparative global miRNA expression profile was determined in human PBMCs and MDMs infected with HIV-1/HIV-2. Differentially expressed miRNAs were identified in HIV-1/HIV-2 infected PBMCs and MDMs using the next-generation sequencing (NGS) technique. A comparative global miRNA expression profile in infected MDMs and PBMCs with HIV-1 and HIV-2 identified differential expression of several host miRNAs. These differentially expressed miRNAs are likely to be involved in many signaling pathways, like the p53 signaling pathway, PI3K-Akt signaling pathways, MAPK signaling pathways, FoxO signaling pathway, and viral carcinogenesis. Thus, a comparative study of the differential expression of host miRNAs in MDMs and T cell in response to HIV-1 and HIV-2 infection will help us to identify unique biomarkers that can differentiate HIV-1 and HIV-2 infection.

Highlights

The Human Immunodeficiency Virus (HIV) is an RNA virus belonging to the genera of lentiviruses, a family of retrovirus that is characterized by its chronic and persistent infection
Reports have indicated that HIV-2 infected patients who progress to AIDS live for a longer time and have relatively higher CD4 counts compared to HIV-1 infected patients who progress to AIDS
RNA samples from Peripheral Blood Mononuclear Cells (PBMCs) isolated from three independent donors productively infected with HIV-1 MN or HIV-2 ROD (Table 1) were used to obtain miRNA expression data from next-generation sequencing (NGS)

Summary

Introduction

The Human Immunodeficiency Virus (HIV) is an RNA virus belonging to the genera of lentiviruses, a family of retrovirus that is characterized by its chronic and persistent infection. HIV-1 and HIV-2 are characterized by a high degree of genetic variation. These viruses closely share common pathways involved in viral transmission, replication, and pathogenesis. These two viruses share many similar characteristics, major differences exist between them. HIV-1 is more virulent, with higher levels of circulating virus than HIV-2. Progression to immunodeficiency is less frequent with HIV-2 infection than with HIV-1 infection, even though the minority who do progress cannot be distinguished clinically from HIV-1 infected patients. HIV-1 is more pathogenic than HIV-2, with higher measurable levels of plasma viremia. The exact mechanisms contributing to these differences is not completely understood

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