Impact of HMGB1/TLR Ligand Complexes on HIV-1 Replication: Possible Role for Flagellin during HIV-1 Infection
Objective. We hypothesized that HMGB1 in complex with bacterial components, such as flagellin, CpG-ODN, and LPS, promotes HIV-1 replication. Furthermore, we studied the levels of antiflagellin antibodies during HIV-1-infection. Methods. Chronically HIV-1-infected U1 cells were stimulated with necrot...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2012-01-01
|
| Series: | International Journal of Microbiology |
| Online Access: | http://dx.doi.org/10.1155/2012/263836 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849408037185388544 |
|---|---|
| author | Piotr Nowak Samir Abdurahman Annica Lindkvist Marius Troseid Anders Sönnerborg |
| author_facet | Piotr Nowak Samir Abdurahman Annica Lindkvist Marius Troseid Anders Sönnerborg |
| author_sort | Piotr Nowak |
| collection | DOAJ |
| description | Objective. We hypothesized that HMGB1 in complex with bacterial components, such as flagellin, CpG-ODN, and LPS, promotes HIV-1 replication. Furthermore, we studied the levels of antiflagellin antibodies during HIV-1-infection. Methods. Chronically HIV-1-infected U1 cells were stimulated with necrotic extract/recombinant HMGB1 in complex with TLR ligands or alone. HIV-1 replication was estimated by p24 antigen in culture supernatants 48–72 hours after stimulation. The presence of systemic anti-flagellin IgG was determined in 51 HIV-1-infected patients and 19 controls by immunoblotting or in-house ELISA. Results. Flagellin, LPS, and CpG-ODN induced stronger HIV-1 replication when incubated together with necrotic extract or recombinant HMGB1 than activation by any of the compounds alone. Moreover, the stimulatory effect of necrotic extract was inhibited by depletion of HMGB1. Elevated levels of anti-flagellin antibodies were present in plasma from HIV-1-infected patients and significantly decreased during 2 years of antiretroviral therapy. Conclusions. Our findings implicate a possible role of HGMB1-bacterial complexes, as a consequence of microbial translocation and cell necrosis, for immune activation in HIV-1 pathogenesis. We propose that flagellin is an important microbial product, that modulates viral replication and induces adaptive immune responses in vivo. |
| format | Article |
| id | doaj-art-3f80c604540f4c49bb27b0beab738751 |
| institution | Kabale University |
| issn | 1687-918X 1687-9198 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | International Journal of Microbiology |
| spelling | doaj-art-3f80c604540f4c49bb27b0beab7387512025-08-20T03:35:53ZengWileyInternational Journal of Microbiology1687-918X1687-91982012-01-01201210.1155/2012/263836263836Impact of HMGB1/TLR Ligand Complexes on HIV-1 Replication: Possible Role for Flagellin during HIV-1 InfectionPiotr Nowak0Samir Abdurahman1Annica Lindkvist2Marius Troseid3Anders Sönnerborg4Department of Infectious Diseases, Institution of Medicine, Karolinska University Hospital and Karolinska Institutet, 14186 Stockholm, SwedenDepartment of Infectious Diseases, Institution of Medicine, Karolinska University Hospital and Karolinska Institutet, 14186 Stockholm, SwedenDepartment of Clinical Microbiology, Institution of Laboratory Medicine, Karolinska University Hospital and Karolinska Institutet, 14186 Stockholm, SwedenDepartment of Infectious Diseases, Oslo University Hospital, Ullevål, 0424 Oslo, NorwayDepartment of Infectious Diseases, Institution of Medicine, Karolinska University Hospital and Karolinska Institutet, 14186 Stockholm, SwedenObjective. We hypothesized that HMGB1 in complex with bacterial components, such as flagellin, CpG-ODN, and LPS, promotes HIV-1 replication. Furthermore, we studied the levels of antiflagellin antibodies during HIV-1-infection. Methods. Chronically HIV-1-infected U1 cells were stimulated with necrotic extract/recombinant HMGB1 in complex with TLR ligands or alone. HIV-1 replication was estimated by p24 antigen in culture supernatants 48–72 hours after stimulation. The presence of systemic anti-flagellin IgG was determined in 51 HIV-1-infected patients and 19 controls by immunoblotting or in-house ELISA. Results. Flagellin, LPS, and CpG-ODN induced stronger HIV-1 replication when incubated together with necrotic extract or recombinant HMGB1 than activation by any of the compounds alone. Moreover, the stimulatory effect of necrotic extract was inhibited by depletion of HMGB1. Elevated levels of anti-flagellin antibodies were present in plasma from HIV-1-infected patients and significantly decreased during 2 years of antiretroviral therapy. Conclusions. Our findings implicate a possible role of HGMB1-bacterial complexes, as a consequence of microbial translocation and cell necrosis, for immune activation in HIV-1 pathogenesis. We propose that flagellin is an important microbial product, that modulates viral replication and induces adaptive immune responses in vivo.http://dx.doi.org/10.1155/2012/263836 |
| spellingShingle | Piotr Nowak Samir Abdurahman Annica Lindkvist Marius Troseid Anders Sönnerborg Impact of HMGB1/TLR Ligand Complexes on HIV-1 Replication: Possible Role for Flagellin during HIV-1 Infection International Journal of Microbiology |
| title | Impact of HMGB1/TLR Ligand Complexes on HIV-1 Replication: Possible Role for Flagellin during HIV-1 Infection |
| title_full | Impact of HMGB1/TLR Ligand Complexes on HIV-1 Replication: Possible Role for Flagellin during HIV-1 Infection |
| title_fullStr | Impact of HMGB1/TLR Ligand Complexes on HIV-1 Replication: Possible Role for Flagellin during HIV-1 Infection |
| title_full_unstemmed | Impact of HMGB1/TLR Ligand Complexes on HIV-1 Replication: Possible Role for Flagellin during HIV-1 Infection |
| title_short | Impact of HMGB1/TLR Ligand Complexes on HIV-1 Replication: Possible Role for Flagellin during HIV-1 Infection |
| title_sort | impact of hmgb1 tlr ligand complexes on hiv 1 replication possible role for flagellin during hiv 1 infection |
| url | http://dx.doi.org/10.1155/2012/263836 |
| work_keys_str_mv | AT piotrnowak impactofhmgb1tlrligandcomplexesonhiv1replicationpossibleroleforflagellinduringhiv1infection AT samirabdurahman impactofhmgb1tlrligandcomplexesonhiv1replicationpossibleroleforflagellinduringhiv1infection AT annicalindkvist impactofhmgb1tlrligandcomplexesonhiv1replicationpossibleroleforflagellinduringhiv1infection AT mariustroseid impactofhmgb1tlrligandcomplexesonhiv1replicationpossibleroleforflagellinduringhiv1infection AT anderssonnerborg impactofhmgb1tlrligandcomplexesonhiv1replicationpossibleroleforflagellinduringhiv1infection |