title: Porphyromonas gingivalis-mediated Epithelial Cell Entry of HIV-1.
abstract: HIV-1 relies on the host's cell machinery to establish a successful infection. Surface receptors, such as CD4, CCR5, and CXCR4 of T cells and macrophages, are essential for membrane fusion of HIV-1, an initiate step in viral entry. However, it is not well defined how HIV-1 infects CD4-negative mucosal epithelial cells. Here we show that there is a specific interaction between HIV-1 and an invasive oral bacterium, Porphyromonas gingivalis. We found that HIV-1 was trapped on the bacterial surface, which led to internalization of HIV-1 virions as the bacteria invaded CD4-negative epithelial cells. Both bacterial and viral DNA was detected in HeLa and TERT-2 cells exposed to the HIV-1-P. gingivalis complexes 2 hr after the initial infection but not in cells exposed to HIV-1 alone. Moreover, epithelial cell entry of HIV-1 was positively correlated with invasive activity of the P. gingivalis strains tested, even when the binding affinities of HIV-1 to these strains were similar. Finally, it was demonstrated that the viral DNA was integrated into the genome of the host epithelial cells. These results reveal a receptor-independent HIV-1 entry into epithelial cells, which may be relevant in HIV transmission in other mucosal epithelia where complex microbial communities can be found.
authors.affiliation: Department of Oral Biology, School of Dentistry, Meharry Medical College, Nashville, TN, USA.
authors.forename: C K
authors.initials: CK
authors.lastname: Mantri
authors.affiliation: Department of Surgery, Duke University Medical Center, Durham, NC, USA hxie@mmc.edu chc@duke.edu.
authors.forename: C
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Microbiology and Immunology, Meharry Medical College, Nashville, TN, USA.
authors.forename: X
authors.initials: X
authors.lastname: Dong
authors.affiliation: Department of Biochemistry and Cancer Biology, Meharry Medical College, Nashville, TN, USA.
authors.forename: J S
authors.initials: JS
authors.lastname: Goodwin
authors.affiliation: Department of Oral Biology, School of Dentistry, Meharry Medical College, Nashville, TN, USA hxie@mmc.edu chc@duke.edu.
authors.forename: H
authors.initials: H
authors.lastname: Xie
mesh_terms: D001431:Bacteriological Techniques; D018929:Cell Culture Techniques; D002460:Cell Line; D002472:Cell Transformation, Viral / Q000502:physiology; D060085:Coinfection; D004847:Epithelial Cells / Q000382:microbiology / Q000821:virology; D015497:HIV-1 / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D015603:Keratinocytes / Q000382:microbiology / Q000821:virology; D056265:Microbial Interactions; D018613:Microscopy, Confocal; D016966:Porphyromonas gingivalis / Q000502:physiology*; D014771:Virion / Q000502:physiology; D053585:Virus Attachment; D014776:Virus Cultivation; D053586:Virus Internalization
keywords: CCR5; CXCR4; HeLA cells; P. gingivalis 33277; TERT-2 cells; bacterial invasion