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-...
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| Veröffentlicht in: | PLoS pathogens 2015-06, Vol.11 (6), p.e1005005-e1005005 |
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| creator | Posch, Wilfried Steger, Marion Knackmuss, Ulla Blatzer, Michael Baldauf, Hanna-Mari Doppler, Wolfgang White, Tommy E Hörtnagl, Paul Diaz-Griffero, Felipe Lass-Flörl, Cornelia Hackl, Hubert Moris, Arnaud Keppler, Oliver T Wilflingseder, Doris |
| 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. |
| doi_str_mv | 10.1371/journal.ppat.1005005 |
| format | Article |
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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.</description><identifier>ISSN: 1553-7374</identifier><identifier>ISSN: 1553-7366</identifier><identifier>EISSN: 1553-7374</identifier><identifier>DOI: 10.1371/journal.ppat.1005005</identifier><identifier>PMID: 26121641</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Acquired immune deficiency syndrome ; AIDS ; CD4-Positive T-Lymphocytes - immunology ; Colleges & universities ; Complement System Proteins - immunology ; Dendritic cells ; Dendritic Cells - immunology ; Experiments ; Gene expression ; HIV ; HIV Infections - immunology ; HIV-1 - immunology ; Human health and pathology ; Human immunodeficiency virus ; Humans ; Infections ; Life Sciences ; Lymphocytes ; Phosphorylation ; Rodents ; Viral infections ; Virus Replication - immunology</subject><ispartof>PLoS pathogens, 2015-06, Vol.11 (6), p.e1005005-e1005005</ispartof><rights>Attribution</rights><rights>2015 Posch et al 2015 Posch et al</rights><rights>2015 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Posch W, Steger M, Knackmuss U, Blatzer M, Baldauf H-M, Doppler W, et al. (2015) Complement-Opsonized HIV-1 Overcomes Restriction in Dendritic Cells. 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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. 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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. 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| subjects | Acquired immune deficiency syndrome AIDS CD4-Positive T-Lymphocytes - immunology Colleges & universities Complement System Proteins - immunology Dendritic cells Dendritic Cells - immunology Experiments Gene expression HIV HIV Infections - immunology HIV-1 - immunology Human health and pathology Human immunodeficiency virus Humans Infections Life Sciences Lymphocytes Phosphorylation Rodents Viral infections Virus Replication - immunology |
| title | Complement-Opsonized HIV-1 Overcomes Restriction in Dendritic Cells |
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