Porphyromonas gingivalis induces CCR5-dependent transfer of infectious HIV-1 from oral keratinocytes to permissive cells.
BACKGROUND
Systemic infection with HIV occurs infrequently through the oral route. The frequency of occurrence may be increased by concomitant bacterial infection of the oral tissues, since co-infection and inflammation of some cell types increases HIV-1 replication. A putative periodontal pathogen, Porphyromonas gingivalis selectively up-regulates expression of the HIV-1 coreceptor CCR5 on oral keratinocytes. We, therefore, hypothesized that P. gingivalis modulates the outcome of HIV infection in oral epithelial cells.


RESULTS
Oral and tonsil epithelial cells were pre-incubated with P. gingivalis, and inoculated with either an X4- or R5-type HIV-1. Between 6 and 48 hours post-inoculation, P. gingivalis selectively increased the infectivity of R5-tropic HIV-1 from oral and tonsil keratinocytes; infectivity of X4-tropic HIV-1 remained unchanged. Oral keratinocytes appeared to harbor infectious HIV-1, with no evidence of productive infection. HIV-1 was harbored at highest levels during the first 6 hours after HIV exposure and decreased to barely detectable levels at 48 hours. HIV did not appear to co-localize with P. gingivalis, which increased selective R5-tropic HIV-1 trans infection from keratinocytes to permissive cells. When CCR5 was selectively blocked, HIV-1 trans infection was reduced.


CONCLUSIONS
P. gingivalis up-regulation of CCR5 increases trans infection of harbored R5-tropic HIV-1 from oral keratinocytes to permissive cells. Oral infections such as periodontitis may, therefore, increase risk for oral infection and dissemination of R5-tropic HIV-1.
Giacaman
Rodrigo A
RA
Department of Diagnostic and Biological Sciences, School of Dentistry, University of Minnesota, Minneapolis, MN 55455, USA. giac0015@umn.edu
Asrani
Anil C
AC
Gebhard
Kristin H
KH
Dietrich
Elizabeth A
EA
Vacharaksa
Anjalee
A
Ross
Karen F
KF
Herzberg
Mark C
MC
D016866:Bacteroidaceae Infections / Q000382:microbiology; D002460:Cell Line; D018920:Coculture Techniques; D004847:Epithelial Cells / Q000276:immunology / Q000821:virology; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D015603:Keratinocytes / Q000382:microbiology*; D009061:Mouth Mucosa / Q000166:cytology / Q000382:microbiology; D016966:Porphyromonas gingivalis / Q000502:physiology*; D019713:Receptors, CCR5 / Q000378:metabolism*; D012307:Risk Factors; D014779:Virus Replication
D019713:Receptors, CCR5