NIAID researchers have helped explain genetic differences that can distinguish some early-transmitting HIVs—viruses found in an infected person within the first month after infection—from forms of HIV isolated later in infection. These genetic features help HIV bind tightly to a molecule called integrin alpha-4 beta-7 (α4β7). According to the scientists, the capacity to bind tightly to α4β7 likely enhances the ability of HIV to complete the many steps of sexual transmission and become the “founder” virus that establishes infection in a person.
The new research also sheds light on CD4 T cells, the primary immune cell targeted by HIV. The HIV surface protein, called gp120, can bind to integrin α4β7 via a receptor that may be present on the surface of the CD4 T cell. The integrin molecule helps direct HIV-infected cells to the intestinal tract, where a vast majority of CD4 T cells reside, allowing the virus to replicate quickly. The scientists believe that CD4 T cells with the α4β7 receptor are likely to play an important role in the sexual transmission of HIV.
This new understanding of the relationship between early-transmitting HIVs, α4β7, and CD4 T cells could advance efforts to design vaccines and other prevention tools to block the virus in the early stages of sexual transmission, before infection takes hold.
Nawaz F, Cicala C, Van Ryk D, Block KE, Jelicic K, McNally JP, Ogundare O, Pascuccio M, Patel N, Wei D, Fauci AS, Arthos J. The genotype of early-transmitting HIV gp120s promotes α (4) β(7)-reactivity, revealing α (4) β(7) +/CD4+ T cells as key targets in mucosal transmission. PLoS Pathog. 2011 Feb;7(2):e1001301.
Last Updated December 28, 2012