Role of Porphyromonas gingivalis outer membrane vesicles in oral mucosal transmission of HIV

Abstract

The association between mucosal microbiota and HIV-1 infection has garnered great attention in the field of HIV-1 research. Previously, we reported a receptor-independent HIV-1 entry into epithelial cells mediated by a Gram-negative invasive bacterium, Porphyromonas gingivalis. Here, we present evidence showing that P. gingivalis outer membrane vesicles (OMVs) promote mucosal transmission of HIV-1. We demonstrated, using the Dynabeads technology, a specific interaction between HIV-1 and P. gingivalis OMVs which led to an OMV-dependent viral entry into oral epithelial cells. HIV-1 was detected in human oral keratinocytes (HOKs) after a 20 minute exposure to the HIV-vesicle complexes. After entry, most of the complexes appeared to dissociate, HIV-1 was reverse-transcribed, and viral DNA was integrated into the genome of HOKs. Meanwhile, some of the complexes exited the original host and re-entered neighboring HOKs and permissive cells of HIV-1. Moreover, P. gingivalis vesicles enhanced HIV-1 infection of MT4 cells at low infecting doses that are not able to establish an efficient infection alone. These findings suggest that invasive bacteria and their OMVs with ability to interact with HIV-1 may serve as a vehicle to translocate HIV through the mucosa, establish mucosal transmission of HIV-1, and enhance HIV-1 infectivity.

Microbiota–host communications: Bacterial extracellular vesicles as a common language

“…In contrast to the defensive role of bacterial EVs described above, they may also facilitate the infection of oral mucosa with other pathogens, such as HIV-1. Dong and colleagues have reported a novel mechanism of HIV-1 entry into nonpermissive cells, in which EVs of P. gingivalis, an invasive oral bacterium, interact specifically with HIV-1 and promote a CD4-independent HIV-1 entry into epithelial cells [83].…”

“…Dong and colleagues have reported a novel mechanism of HIV-1 entry into nonpermissive cells, in which EVs of P . gingivalis , an invasive oral bacterium, interact specifically with HIV-1 and promote a CD4-independent HIV-1 entry into epithelial cells [ 83 ].…”

Vesiduction: the fourth way of HGT

“…In other cases, they can constitute the secretion pathway of enzymes involved in the degradation of complex substrates, as it has been shown for the degradation of cellulose by Bacteroides in the rumen (Forsberg et al, 1981). Recently, EVs secreted by Porphyromonas gingivalis were shown to promote HIV-1 transmission through oral mucosa (Dong et al, 2018). To date, the accumulation of data concerning EVs suggests that they are widespread in nature: they have been observed in domestic biofilms, in freshwater as well as in the ocean (Schooling and Beveridge, 2006;Biller et al, 2014).…”

Outer membrane vesicles of Porphyromonas gingivalis: Novel communication tool and strategy

“…P. gingivalis OMVs promote mucosal transmission of HIV-1. Dynabeads technology showed that a specific interaction between HIV-1 and P. gingivalis OMVs supports viral entry into oral epithelial cells [ 70 ]. Subsequently, HIV-1 was reverse-transcribed and viral DNA was integrated into the genome of these cells.…”

“…Recent studies using genetic, proteomic, and morphological tools have demonstrated that P. gingivalis OMVs include a variety of virulence factors provided by parental cells [ 70 ]. As described above, P. gingivalis OMVs possess various components of outer membrane constituents, including LPS, muramic acid, a capsule, fimbriae, and gingipains [ 41 , 42 ].…”