title: Porphyromonas gingivalis-mediated signaling through TLR4 mediates persistent HIV infection of primary macrophages.
abstract: Periodontal infections contribute to HIV-associated co-morbidities in the oral cavity and provide a model to interrogate the dysregulation of macrophage function, inflammatory disease progression, and HIV replication during co-infections. We investigated the effect of Porphyromonas gingivalis on the establishment of HIV infection in monocyte-derived macrophages. HIV replication in macrophages was significantly repressed in the presence of P. gingivalis. This diminished viral replication was due partly to a decrease in the expression of integrated HIV provirus. HIV repression depended upon signaling through TLR4 as knock-down of TLR4 with siRNA rescued HIV expression. Importantly, HIV expression was reactivated upon removal of P. gingivalis. Our observations suggest that exposure of macrophages to Gram-negative bacteria influence the establishment and maintenance of HIV persistence in macrophages through a TLR4-dependent mechanism.
authors.affiliation: Department of Medicine, Section of Infectious Diseases, Boston Medical Center, Boston, MA, USA. Electronic address: agosto@bu.edu.
authors.forename: Luis M
authors.initials: LM
authors.lastname: Agosto
authors.affiliation: Department of Microbiology, Boston University School of Medicine, Boston, MA, USA.
authors.forename: Juliane B
authors.initials: JB
authors.lastname: Hirnet
authors.affiliation: Department of Medicine, Section of Infectious Diseases, Boston Medical Center, Boston, MA, USA.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Michaels
authors.affiliation: Department of Medicine, Section of Infectious Diseases, Boston Medical Center, Boston, MA, USA.
authors.forename: Yazdani B
authors.initials: YB
authors.lastname: Shaik-Dasthagirisaheb
authors.affiliation: Department of Oral Biology, College of Dentistry, University of Florida, Gainesville, FL 32610-0424, USA.
authors.forename: Frank C
authors.initials: FC
authors.lastname: Gibson
authors.affiliation: Department of Microbiology, Boston University School of Medicine, Boston, MA, USA.
authors.forename: Gregory
authors.initials: G
authors.lastname: Viglianti
authors.affiliation: Department of Medicine, Section of Infectious Diseases, Boston Medical Center, Boston, MA, USA; Department of Microbiology, Boston University School of Medicine, Boston, MA, USA. Electronic address: andrew.henderson@bmc.org.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Henderson
mesh_terms: D000954:Antigens, Surface / Q000378:metabolism; D015967:Gene Expression Regulation, Viral; D055785:Gene Knockdown Techniques; D015658:HIV Infections / Q000276:immunology / Q000378:metabolism* / Q000821:virology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D016130:Immunophenotyping; D007963:Leukocytes, Mononuclear; D008264:Macrophages / Q000276:immunology / Q000378:metabolism* / Q000821:virology*; D056265:Microbial Interactions; D010641:Phenotype; D016966:Porphyromonas gingivalis / Q000502:physiology*; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication
chemical_list: D000954:Antigens, Surface; D051197:Toll-Like Receptor 4