Integrin α4β7 in HIV-1 infection: A critical review.
Over the past decade, a series of observations linking α4β7, the principal gut-homing integrin, with various aspects of HIV-1 infection have generated considerable interest in the field of HIV-1 research. After the initial report that the major HIV-1 envelope glycoprotein, gp120, can bind to α4β7, intensive research efforts have been focused on the role of α4β7 as a key factor in HIV-1 pathogenesis and as a potential target for prevention and treatment. The interaction between α4β7 and its natural ligand, MAdCAM-1, directs infected CD4+ T cells and HIV-1 virions carrying incorporated α4β7 to the gut mucosa, which may facilitate HIV-1 seeding and replication in the intestinal compartment during the early stages of infection. In addition, cells that express high levels of α4β7, such as Th17 cells, represent preferential targets for infection, and their frequency in the circulation was shown to correlate with susceptibility to HIV-1 infection and disease progression. A number of in vivo studies in nonhuman primates have investigated whether blockage of α4β7 may affect SIV transmission and pathogenesis. Administration of a primatized anti-α4β7 antibody that blocks MAdCAM-1 binding to α4β7 was reported to reduce SIV mucosal transmission in rhesus macaques. However, the mechanism responsible for such a protective effect is still undefined, and conflicting results have been reported on the effects of the same antibody, in combination with ART, during the early chronic phase of SIV infection. Thus, despite a series of tantalizing results accrued over the past decade, the jury is still out on the role of α4β7 in HIV-1 infection.
['Liu|Qingbo|Q|', 'Lusso|Paolo|P|0000-0002-2813-4081']
D000818:Animals D015699:HIV Envelope Protein gp120 D015658:HIV Infections D015497:HIV-1 D054884:Host-Pathogen Interactions D006801:Humans D016023:Integrins D011485:Protein Binding D011991:Receptors, Virus D016176:T-Lymphocyte Subsets D014779:Virus Replication
α4β7 HIV-1 infection anti-α4β7 therapy gut homing