Species tropism of HIV-1 modulated by viral accessory proteins

Abstract

Human immunodeficiency virus type 1 (HIV-1) is tropic and pathogenic only for humans, and does not replicate in macaque monkeys routinely used for experimental infections. This specially narrow host range (species tropism) has impeded much the progress of HIV-1/acquired immunodeficiency syndrome (AIDS) basic research. Extensive studies on the underlying mechanism have revealed that Vif, one of viral accessory proteins, is critical for the HIV-1 species tropism in addition to Gag-capsid protein. Another auxiliary protein Vpu also has been demonstrated to affect this HIV-1 property. In this review, we focus on functional interactions of these HIV-1 proteins and species specific-restriction factors. In addition, we describe an evolutional viewpoint that is relevant to the species tropism of HIV-1 controlled by the accessory proteins.

Keywords: HIV-1; Vif; Vpu; accessory protein; species tropism.

FIGURE 1

Genome organization of primate immunodeficiency viruses. Various proviral genomes are schematically shown. As indicated by colored boxes, the vpr and vpu genes of SIVcpz/HIV-1 came from those of SIVrcm and SIVmon/mus/gsn, respectively. Also, the vif genes of SIVcpz/HIV-1 originated from that of SIVrcm. In addition, as shown by colored boxes, HIV-1 nef gene is similar to but distinct from SIVcpz nef gene. HIV-1 nef gene is different from those of SIVmon/mus/gsn, SIVrcm, and HIV-2 as indicated. For virus designations, see text.

FIGURE 2

A schema of replication kinetics by HIV-1 wild-type and mutant viruses. Viral growth properties in cells are illustrated based on numerous infection experiments in our laboratory. WT, wild-type.

FIGURE 3

HIV-1 replication and APOBEC3G. On the basis of results reported so far, the action mechanism of Vif is depicted. Replication process for wild-type (WT) and ΔVif mutant viruses are schematically shown on the basis of previously reported review articles (Holmes et al., 2007; Huthoff and Towers, 2008; Strebel et al., 2009). A3G, APOBEC3G; IN, viral integrase protein.

FIGURE 4

HIV-1 replication and Tetherin. On the basis of results reported so far, the action mechanism of Vpu is depicted. Replication process for wild-type (WT) and ΔVpu mutant viruses are schematically shown on the basis of previously reported review articles (Tokarev et al., 2009; Douglas et al., 2010; Evans et al., 2010). TGN, trans-Golgi network.