Complement-Opsonized HIV-1 Overcomes Restriction in Dendritic Cells.
DCs express intrinsic cellular defense mechanisms to specifically inhibit HIV-1 replication. Thus, DCs are productively infected only at very low levels with HIV-1, and this non-permissiveness of DCs is suggested to go along with viral evasion. We now illustrate that complement-opsonized HIV-1 (HIV-...
Saved in:
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2015-06-01
|
| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1005005 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850125514628399104 |
|---|---|
| author | Wilfried Posch Marion Steger Ulla Knackmuss Michael Blatzer Hanna-Mari Baldauf Wolfgang Doppler Tommy E White Paul Hörtnagl Felipe Diaz-Griffero Cornelia Lass-Flörl Hubert Hackl Arnaud Moris Oliver T Keppler Doris Wilflingseder |
| author_facet | Wilfried Posch Marion Steger Ulla Knackmuss Michael Blatzer Hanna-Mari Baldauf Wolfgang Doppler Tommy E White Paul Hörtnagl Felipe Diaz-Griffero Cornelia Lass-Flörl Hubert Hackl Arnaud Moris Oliver T Keppler Doris Wilflingseder |
| author_sort | Wilfried Posch |
| collection | DOAJ |
| description | DCs express intrinsic cellular defense mechanisms to specifically inhibit HIV-1 replication. Thus, DCs are productively infected only at very low levels with HIV-1, and this non-permissiveness of DCs is suggested to go along with viral evasion. We now illustrate that complement-opsonized HIV-1 (HIV-C) efficiently bypasses SAMHD1 restriction and productively infects DCs including BDCA-1 DCs. Efficient DC infection by HIV-C was also observed using single-cycle HIV-C, and correlated with a remarkable elevated SAMHD1 T592 phosphorylation but not SAMHD1 degradation. If SAMHD1 phosphorylation was blocked using a CDK2-inhibitor HIV-C-induced DC infection was also significantly abrogated. Additionally, we found a higher maturation and co-stimulatory potential, aberrant type I interferon expression and signaling as well as a stronger induction of cellular immune responses in HIV-C-treated DCs. Collectively, our data highlight a novel protective mechanism mediated by complement opsonization of HIV to effectively promote DC immune functions, which might be in the future exploited to tackle HIV infection. |
| format | Article |
| id | doaj-art-3229697ce79b486096be3740177f757b |
| institution | OA Journals |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2015-06-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-3229697ce79b486096be3740177f757b2025-08-20T02:34:06ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742015-06-01116e100500510.1371/journal.ppat.1005005Complement-Opsonized HIV-1 Overcomes Restriction in Dendritic Cells.Wilfried PoschMarion StegerUlla KnackmussMichael BlatzerHanna-Mari BaldaufWolfgang DopplerTommy E WhitePaul HörtnaglFelipe Diaz-GrifferoCornelia Lass-FlörlHubert HacklArnaud MorisOliver T KepplerDoris WilflingsederDCs express intrinsic cellular defense mechanisms to specifically inhibit HIV-1 replication. Thus, DCs are productively infected only at very low levels with HIV-1, and this non-permissiveness of DCs is suggested to go along with viral evasion. We now illustrate that complement-opsonized HIV-1 (HIV-C) efficiently bypasses SAMHD1 restriction and productively infects DCs including BDCA-1 DCs. Efficient DC infection by HIV-C was also observed using single-cycle HIV-C, and correlated with a remarkable elevated SAMHD1 T592 phosphorylation but not SAMHD1 degradation. If SAMHD1 phosphorylation was blocked using a CDK2-inhibitor HIV-C-induced DC infection was also significantly abrogated. Additionally, we found a higher maturation and co-stimulatory potential, aberrant type I interferon expression and signaling as well as a stronger induction of cellular immune responses in HIV-C-treated DCs. Collectively, our data highlight a novel protective mechanism mediated by complement opsonization of HIV to effectively promote DC immune functions, which might be in the future exploited to tackle HIV infection.https://doi.org/10.1371/journal.ppat.1005005 |
| spellingShingle | Wilfried Posch Marion Steger Ulla Knackmuss Michael Blatzer Hanna-Mari Baldauf Wolfgang Doppler Tommy E White Paul Hörtnagl Felipe Diaz-Griffero Cornelia Lass-Flörl Hubert Hackl Arnaud Moris Oliver T Keppler Doris Wilflingseder Complement-Opsonized HIV-1 Overcomes Restriction in Dendritic Cells. PLoS Pathogens |
| title | Complement-Opsonized HIV-1 Overcomes Restriction in Dendritic Cells. |
| title_full | Complement-Opsonized HIV-1 Overcomes Restriction in Dendritic Cells. |
| title_fullStr | Complement-Opsonized HIV-1 Overcomes Restriction in Dendritic Cells. |
| title_full_unstemmed | Complement-Opsonized HIV-1 Overcomes Restriction in Dendritic Cells. |
| title_short | Complement-Opsonized HIV-1 Overcomes Restriction in Dendritic Cells. |
| title_sort | complement opsonized hiv 1 overcomes restriction in dendritic cells |
| url | https://doi.org/10.1371/journal.ppat.1005005 |
| work_keys_str_mv | AT wilfriedposch complementopsonizedhiv1overcomesrestrictionindendriticcells AT marionsteger complementopsonizedhiv1overcomesrestrictionindendriticcells AT ullaknackmuss complementopsonizedhiv1overcomesrestrictionindendriticcells AT michaelblatzer complementopsonizedhiv1overcomesrestrictionindendriticcells AT hannamaribaldauf complementopsonizedhiv1overcomesrestrictionindendriticcells AT wolfgangdoppler complementopsonizedhiv1overcomesrestrictionindendriticcells AT tommyewhite complementopsonizedhiv1overcomesrestrictionindendriticcells AT paulhortnagl complementopsonizedhiv1overcomesrestrictionindendriticcells AT felipediazgriffero complementopsonizedhiv1overcomesrestrictionindendriticcells AT cornelialassflorl complementopsonizedhiv1overcomesrestrictionindendriticcells AT huberthackl complementopsonizedhiv1overcomesrestrictionindendriticcells AT arnaudmoris complementopsonizedhiv1overcomesrestrictionindendriticcells AT olivertkeppler complementopsonizedhiv1overcomesrestrictionindendriticcells AT doriswilflingseder complementopsonizedhiv1overcomesrestrictionindendriticcells |