Review
Copyright ©2014 Baishideng Publishing Group Inc. All rights reserved.
World J Immunol. Jul 27, 2014; 4(2): 107-115
Published online Jul 27, 2014. doi: 10.5411/wji.v4.i2.107
Role of host immune responses in sequence variability of HIV-1 Vpu
Zafrul Hasan, Doreen Kamori, Takamasa Ueno
Zafrul Hasan, Doreen Kamori, Takamasa Ueno, Center for AIDS Research, Kumamoto University, Kumamoto 860-0811, Japan
Takamasa Ueno, International Research Center for Medical Sciences (IRCMS), Kumamoto University, Kumamoto 860-0811, Japan
Author contributions: Hasan Z and Kamori D contributed equally to this work; Hasan Z and Kamori D generated the figures and wrote the manuscript; Ueno T designed the study and contributed to the writing of the manuscript.
Supported by A Grant-in-Aid for Scientific Research from the Ministry of Education, Science, Sports, and Culture (MEXT) of Japan; and A Grant-in-Aid for AIDS Research from the Ministry of Health, Labor, and Welfare of Japan; The Scholarship for the International Priority Graduate Programs, to Hasan Z and Kamori D; Advanced Graduate Courses for International Students (Doctoral Course), MEXT, Japan, to Hasan Z and Kamori D
Correspondence to: Takamasa Ueno, PhD, Center for AIDS Research, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan. uenotaka@kumamoto-u.ac.jp
Telephone: +81-96-3736826 Fax: +81-96-3736825
Received: March 7, 2014
Revised: April 19, 2014
Accepted: June 14, 2014
Published online: July 27, 2014
Processing time: 142 Days and 5 Hours
Abstract

Viral protein U (Vpu) is an accessory protein associated with two main functions important in human immunodeficiency virus type 1 (HIV-1) replication and dissemination; these are down-regulation of CD4 receptor through mediating its proteasomal degradation and enhancement of virion release by antagonizing tetherin/BST2. It is also well established that Vpu is one of the most highly variable proteins in the HIV-1 proteome. However it is still unclear what drives Vpu sequence variability, whether Vpu acquires polymorphisms as a means of immune escape, functional advantage, or otherwise. It is assumed that the host-pathogen interaction is a cause of polymorphic phenotype of Vpu and that the resulting functional heterogeneity of Vpu may have critical significance in vivo. In order to comprehensively understand Vpu variability, it is important to integrate at the population level the genetic association approaches to identify specific amino acid residues and the immune escape kinetics which may impose Vpu functional constraints in vivo. This review will focus on HIV-1 accessory protein Vpu in the context of its sequence variability at population level and also bring forward evidence on the role of the host immune responses in driving Vpu sequence variability; we will also highlight the recent findings that illustrate Vpu functional implication in HIV-1 pathogenesis.

Keywords: Human immunodeficiency virus type 1; Vpu; Sequence variability; Immune responses; Human leukocyte antigen class I

Core tip: Viral protein U (Vpu) is a highly polymorphic human immunodeficiency virus type 1 (HIV-1) accessory protein; however factors that are attributable to Vpu sequence variability are not well defined. In this review we have focused on the immune responses both innate (natural killer cells) and adaptive (cellular and humoral) immunity that are directed towards HIV-1 Vpu and we also show the interaction between Vpu and host cellular factors. We also highlight evidence that suggests interaction between the host immune responses and Vpu may contribute to Vpu sequence variability. Finally we have summarized the current knowledge on HIV-1 Vpu functions including Vpu evasion activities from the host immune surveillance.