Primary intestinal epithelial cells selectively transfer R5 HIV-1 to CCR5+ cells.
The upper gastrointestinal tract is a principal route of HIV-1 entry in vertical transmission and after oral-genital contact. The phenotype of the newly acquired virus is predominantly R5 (CCR5-tropic) and not X4 (CXCR4-tropic), although both R5 and X4 viruses are frequently inoculated onto the mucosa. Here we show that primary intestinal (jejunal) epithelial cells express galactosylceramide, an alternative primary receptor for HIV-1, and CCR5 but not CXCR4. Moreover, we show that intestinal epithelial cells transfer R5, but not X4, viruses to CCR5+ indicator cells, which can efficiently replicate and amplify virus expression. Transfer was remarkably efficient and was not inhibited by the fusion blocker T-20, but was substantially reduced by colchicine and low (4 degrees C) temperature, suggesting endocytotic uptake and microtubule-dependent transcytosis of HIV-1. Our finding that CCR5+ intestinal epithelial cells select and transfer exclusively R5 viruses indicates a mechanism for the selective transmission of R5 HIV-1 in primary infection acquired through the upper gastrointestinal tract.
Meng
Gang
G
Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Wei
Xiping
X
Wu
Xiaoyun
X
Sellers
Marty T
MT
Decker
Julie M
JM
Moldoveanu
Zina
Z
Orenstein
Jan M
JM
Graham
Martin F
MF
Kappes
John C
JC
Mestecky
Jiri
J
Shaw
George M
GM
Smith
Phillip D
PD
D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000737:chemistry; D015700:HIV Envelope Protein gp41 / Q000737:chemistry / Q000235:genetics; D015658:HIV Infections / Q000276:immunology* / Q000635:transmission; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D018928:Immunity, Mucosal; D018445:Infectious Disease Transmission, Vertical; D007413:Intestinal Mucosa / Q000276:immunology / Q000821:virology*; D007583:Jejunum; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics; D019713:Receptors, CCR5 / Q000737:chemistry / Q000276:immunology*; D015728:Receptors, HIV / Q000276:immunology*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
D019380:Anti-HIV Agents; D015700:HIV Envelope Protein gp41; D010446:Peptide Fragments; D019713:Receptors, CCR5; D015728:Receptors, HIV; C407148:peptide N36