How HIV Hijacks the Cellular Protein Alpha-4 Beta-7
During the early stages of infection, HIV mounts a severe and prolonged attack on the gut, which harbors a rich population of CD4+ T cells—the main type of immune cell that HIV infects and destroys. These cells are directed to and retained in the gut through the action of a protein on their surfaces called alpha-4 beta-7 integrin.
Earlier this year, NIAID scientists reported that alpha-4 beta-7 also is present on the surface of HIV itself. When newly forming HIV emerges from an infected cell producing alpha-4 beta-7, it carries the integrin along and incorporates it into its viral membrane. Like immune cells bearing alpha-4 beta-7, HIV bearing this protein is directed into and retained in the immune tissues in the gut. In this way, the virus hijacks a cellular protein to sharpen its assault on the immune system. Watch a two-minute animation describing the process:
These insights help explain earlier findings showing that treatment with an antibody targeting alpha-4 beta-7 led to sustained viral remission in monkeys infected with an HIV-like virus. NIAID researchers now are conducting an early-stage clinical trial in humans to determine whether short-term treatment with the anti-alpha-4 beta-7 antibody vedolizumab, which is FDA-approved to treat inflammatory bowel diseases, can induce sustained viral remission in people living with HIV.
Reference: C Guzzo, D Ichikawa et al. Virion incorporation of integrin α4β7 facilitates HIV-1 infection and intestinal homing. Science Immunology DOI: 10.1126/sciimmunol.aam7341 (2017)