Complement Opsonization of HIV-1 Enhances the Uptake by Dendritic Cells and Involves the Endocytic Lectin and Integrin Receptor Families
Interaction with the complement system is an underappreciated aspect of HIV-1 infection; even in primary infection, complement fragments are found on virions with potential to affect the interplay between the virus and dendritic cells (DC). Since opsonization may affect the efficiency of uptake and...
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| Format: | Online |
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Public Library of Science
2011
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3154940/ |
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pubmed-31549402011-08-18 Complement Opsonization of HIV-1 Enhances the Uptake by Dendritic Cells and Involves the Endocytic Lectin and Integrin Receptor Families Tjomsland, Veronica Ellegård, Rada Che, Karlhans Hinkula, Jorma Lifson, Jeffrey D. Larsson, Marie Research Article Interaction with the complement system is an underappreciated aspect of HIV-1 infection; even in primary infection, complement fragments are found on virions with potential to affect the interplay between the virus and dendritic cells (DC). Since opsonization may affect the efficiency of uptake and the type of receptors utilized, we compared the interactions of DC with free HIV-1 (F-HIV) and complement opsonized HIV-1 (C-HIV). We demonstrate that C-HIV significantly enhanced the uptake by immature DC (IDC) and mature DC (MDC) and that the internalization rate was dependent on both opsonization of the virus and DC maturation state. Increased DC uptake of C-HIV was not due to opsonization related increased binding of virus to the surface of DC but rather increased internalization of C-HIV despite utilizing a similar repertoire of receptors as F-HIV. Both F-HIV and C-HIV interacted with C-type lectins, integrins, and CD4 and blocking these receptor families prevented HIV-1 from binding to DC at 4°C. Blocking integrins significantly reduced the binding and uptake of F-HIV and C-HIV implicating the involvement of several integrins such as β1-integrin, CR3, LFA-1, and α4β7. Distinctive for C-HIV was usage of β1-integrin and for F-HIV, usage of β7-integrin, whereas both F-HIV and C-HIV utilized both integrin chains of CR3. We have in this study identified the receptor types used by both F-HIV and C-HIV to bind to DC. Noteworthy, C-HIV was internalized more efficiently by DC than F-HIV, probably via receptor mediated endocytosis, which may entail different intracellular processing of the virus leading to both elevated infection and altered activation of HIV specific immune responses. Public Library of Science 2011-08-11 /pmc/articles/PMC3154940/ /pubmed/21853149 http://dx.doi.org/10.1371/journal.pone.0023542 Text en Tjomsland et al. http://creativecommons.org/licenses/by/4.0/ 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 properly credited. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Tjomsland, Veronica Ellegård, Rada Che, Karlhans Hinkula, Jorma Lifson, Jeffrey D. Larsson, Marie |
| spellingShingle |
Tjomsland, Veronica Ellegård, Rada Che, Karlhans Hinkula, Jorma Lifson, Jeffrey D. Larsson, Marie Complement Opsonization of HIV-1 Enhances the Uptake by Dendritic Cells and Involves the Endocytic Lectin and Integrin Receptor Families |
| author_facet |
Tjomsland, Veronica Ellegård, Rada Che, Karlhans Hinkula, Jorma Lifson, Jeffrey D. Larsson, Marie |
| author_sort |
Tjomsland, Veronica |
| title |
Complement Opsonization of HIV-1 Enhances the Uptake by Dendritic Cells and Involves the Endocytic Lectin and Integrin Receptor Families |
| title_short |
Complement Opsonization of HIV-1 Enhances the Uptake by Dendritic Cells and Involves the Endocytic Lectin and Integrin Receptor Families |
| title_full |
Complement Opsonization of HIV-1 Enhances the Uptake by Dendritic Cells and Involves the Endocytic Lectin and Integrin Receptor Families |
| title_fullStr |
Complement Opsonization of HIV-1 Enhances the Uptake by Dendritic Cells and Involves the Endocytic Lectin and Integrin Receptor Families |
| title_full_unstemmed |
Complement Opsonization of HIV-1 Enhances the Uptake by Dendritic Cells and Involves the Endocytic Lectin and Integrin Receptor Families |
| title_sort |
complement opsonization of hiv-1 enhances the uptake by dendritic cells and involves the endocytic lectin and integrin receptor families |
| description |
Interaction with the complement system is an underappreciated aspect of HIV-1 infection; even in primary infection, complement fragments are found on virions with potential to affect the interplay between the virus and dendritic cells (DC). Since opsonization may affect the efficiency of uptake and the type of receptors utilized, we compared the interactions of DC with free HIV-1 (F-HIV) and complement opsonized HIV-1 (C-HIV). We demonstrate that C-HIV significantly enhanced the uptake by immature DC (IDC) and mature DC (MDC) and that the internalization rate was dependent on both opsonization of the virus and DC maturation state. Increased DC uptake of C-HIV was not due to opsonization related increased binding of virus to the surface of DC but rather increased internalization of C-HIV despite utilizing a similar repertoire of receptors as F-HIV. Both F-HIV and C-HIV interacted with C-type lectins, integrins, and CD4 and blocking these receptor families prevented HIV-1 from binding to DC at 4°C. Blocking integrins significantly reduced the binding and uptake of F-HIV and C-HIV implicating the involvement of several integrins such as β1-integrin, CR3, LFA-1, and α4β7. Distinctive for C-HIV was usage of β1-integrin and for F-HIV, usage of β7-integrin, whereas both F-HIV and C-HIV utilized both integrin chains of CR3. We have in this study identified the receptor types used by both F-HIV and C-HIV to bind to DC. Noteworthy, C-HIV was internalized more efficiently by DC than F-HIV, probably via receptor mediated endocytosis, which may entail different intracellular processing of the virus leading to both elevated infection and altered activation of HIV specific immune responses. |
| publisher |
Public Library of Science |
| publishDate |
2011 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3154940/ |
| _version_ |
1611470575892430848 |