gp340 expressed on human genital epithelia binds HIV-1 envelope protein and facilitates viral transmission.
During sexual transmission of HIV in women, the first cells likely to be infected are submucosal CD4(+) T cells and dendritic cells of the lower genital tract. HIV is segregated from these target cells by an epithelial cell layer that can be bypassed even when healthy and intact. To understand how HIV penetrates this barrier, we identified a host protein, gp340, that is expressed on genital epithelium and binds the HIV envelope via a specific protein-protein interaction. This binding allows otherwise subinfectious amounts of HIV to efficiently infect target cells and allows this infection to occur over a longer period of time after binding. Our findings suggest a mechanism of viral entry during heterosexual transmission where HIV is bound to intact genital epithelia, which then promotes the initial events of infection. Understanding this step in the initiation of infection will allow for the development of tools and methods for blocking HIV transmission.
Stoddard
Earl
E
Department of Medicine, Division of Infectious Diseases, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Cannon
Georgetta
G
Ni
Houping
H
Karikó
Katalin
K
Capodici
John
J
Malamud
Daniel
D
Weissman
Drew
D
D002135:Calcium-Binding Proteins; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D002478:Cells, Cultured; D002584:Cervix Uteri / Q000737:chemistry / Q000378:metabolism* / Q000821:virology; D004268:DNA-Binding Proteins; D004848:Epithelium / Q000737:chemistry / Q000378:metabolism / Q000821:virology; D005260:Female; D015658:HIV Infections / Q000378:metabolism / Q000635:transmission*; D015497:HIV-1; D006801:Humans; D011956:Receptors, Cell Surface / Q000032:analysis / Q000378:metabolism*; D025521:Tumor Suppressor Proteins; D014621:Vagina / Q000737:chemistry / Q000378:metabolism* / Q000821:virology; D014759:Viral Envelope Proteins / Q000378:metabolism*
D002135:Calcium-Binding Proteins; C108174:DMBT1 protein, human; D004268:DNA-Binding Proteins; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins; D014759:Viral Envelope Proteins