Content area
Full Text
About the Authors:
Muhammad Atif Zahoor
Contributed equally to this work with: Muhammad Atif Zahoor, Guangai Xue
Affiliations Viral Infectious Diseases Unit, RIKEN, Wako, Saitama, Japan, Japanese Foundation of AIDS Prevention, Tokyo, Japan
Guangai Xue
Contributed equally to this work with: Muhammad Atif Zahoor, Guangai Xue
Affiliations Viral Infectious Diseases Unit, RIKEN, Wako, Saitama, Japan, Japanese Foundation of AIDS Prevention, Tokyo, Japan
Hirotaka Sato
Affiliation: Viral Infectious Diseases Unit, RIKEN, Wako, Saitama, Japan
Tomoyuki Murakami
Affiliation: Viral Infectious Diseases Unit, RIKEN, Wako, Saitama, Japan
Shin-nosuke Takeshima
Affiliation: Viral Infectious Diseases Unit, RIKEN, Wako, Saitama, Japan
Yoko Aida
* E-mail: [email protected]
Affiliation: Viral Infectious Diseases Unit, RIKEN, Wako, Saitama, Japan
Introduction
Antigen-presenting cells (APCs) are critical for both innate and adaptive immunity. Professional APCs such as macrophages play an integral role in the immune pathogenesis of the human immunodeficiency virus type 1 (HIV-1) [1]. HIV-1 is a member of the lentivirus family and is the etiologic agent of acquired immunodeficiency syndrome (AIDS). It interacts with host cells through multiple signaling pathways to establish the disease [2]. The infection involves complex mechanisms through which HIV-1 overcomes the host immune responses and causes reprogramming of the host transcriptome and proteome [3]–[5].
Vpr, an accessory gene product of HIV-1, is a protein of 96 amino acids and has a predicted molecular weight of 15 kDa that is relatively conserved in HIV-1 and simian immunodeficiency virus (SIV) [6]. Vpr is a pleiotropic protein that is involved in diverse functions including cell-cycle arrest at the G2/M phase [7], apoptosis [7]–[9], nuclear import of the pre-integration complex [10]–[14], transcriptional activation [15], and splicing [16], [17]. Vpr performs these functions through interactions with various host cellular factors such as DCAF1, SAP145, p300, and importin-α [8], [10], [11], .
A striking feature of Vpr is its unique potential to promote viral productivity in monocytes/macrophages and in a small population of CD4+ T-cells [22]–[26]. Although Vpr is thought to play an important role in HIV-1-infected human macrophages [1], [3], [6], [11], [21], [23], little is known about how it disrupts the expression profile of host cellular genes. In this study, we analyzed the effect of Vpr on the expression profiles of host cellular genes in human monocyte-derived macrophages (MDMs), with the idea that...