Transmission of Immunodeficiency Viruses: Dendritic Cells and Innate and Adaptive Immune Responses
Understanding how human immunodeficiency virus (HIV) is transmitted during sexual intercourse and how co-pathogens impact HIV spread is a focus of Council research.
The human immunodeficiency virus (HIV) is predominantly transmitted across the body surfaces of the genital, rectal, and oral cavities. Cells within these tissues likely contribute to virus capture and the initiation of infection. A particular type of white blood cell, the dendritic cell, is one of the first white blood cells to encounter the virus. The normal function of dendritic cells in the immune system is to capture pathogens and present them to the immune system to activate protective immunity, however, this does not occur successfully in the face of HIV, and, in fact, HIV exploits the dendritic cell system.
Dendritic cells easily capture HIV (entrapping it and becoming infected by it) and can rapidly spread infection to the more susceptible CD4 T cells, readily amplifying virus spread. Moreover, HIV can modify the functions of dendritic cells to favor virus spread over immune activation to clear infection.
The biology of dendritic cell–virus interactions is being studied to improve our understanding of these events.
Council researchers are exploring how interactions with other cell types (e.g., T cells and epithelial cells) influence this biology and how HIV subverts normal dendritic cell-driven immunity to promote infection. Novel strategies are being tested for their ability to activate mucosal dendritic cells in vitro and in vivo in order to suppress virus growth while boosting immunity. Because herpes simplex virus (HSV) increases HIV transmission, researchers are also studying whether HSV-induced changes in dendritic cell function facilitate enhanced HIV spread across the mucosa. Another common co-pathogen, Candida albicans, also alters dendritic cell-driven HIV infection, and studies continue to explore how this might influence HIV transmission. This research will help advance strategies to prevent HIV transmission through microbicides (and possibly vaccines).
See also: Robbiani laboratory
Attachment and fusion inhibitors potently prevent DC-driven infection (abstract) (PDF)
Frank,Ines; Robbiani,Melissa
Journal of Acquired Immune Deficiency Syndromes 56(3): 204-212
Publication date: 2011
Candida albicans-induced DC activation reduces HIV amplification by DCs while increasing DC-to-T-cell spread of HIV (abstract) (HTML)
Vachot,Laurence; Williams,Vennansha G.; Bess Jr.,Julian W.; Lifson,Jeffrey D.; Robbiani,Melissa
Journal of Acquired Immune Deficiency Syndromes 48(4): 398-407
Publication date: 2008
A fusion inhibitor prevents spread of immunodeficiency viruses, but not activation of virus-specific T cells, by dendritic cells (abstract) (PDF) (HTML)
Frank,Ines; Stoessel,Hella; Gettie,Agegnehu; Turville,Stuart G.; Bess Jr.,Julian W.; Lifson,Jeffrey D.; Sivin,Irving; Romani,Nikolaus; Robbiani,Melissa
Journal of Virology 82(11): 5329-5339
Publication date: 2008
CD4-specific Designed Ankyrin Repeat Proteins are novel potent HIV entry inhibitors with unique characteristics (abstract) (PDF)
Schweizer,Andreas; Rusert,Peter; Berlinger,Livia; Ruprecht,Claudia R.; Mann,Axel; Corthesy,Stephanie; Turville,Stuart G.; Aravantinou,Meropi; Fischer,Marek; Robbiani,Melissa; Amstutz,Patrick; Trkola,Alexandra
PLoS Pathogens 4(7): e1000109-
Publication date: 2008
Efficacy of Carraguard-based microbicides in vivo despite variable in vitro activity (abstract) (PDF)
Turville,Stuart G.; Aravantinou,Meropi; Miller,Todd; Kenney,Jessica; Teitelbaum,Aaron; Hu,Lieyu; Chudolij,Anne; Zydowsky,Thomas M.; Piatak Jr.,Michael; Bess Jr.,Julian W.; Lifson,Jeffrey D.; Blanchard,James; Gettie,Agegnehu; Robbiani,Melissa
PLoS ONE 3(9): e3162-
Publication date: 2008
Feline immunodeficiency virus dendritic cell infection and transfer (abstract) (PDF) (HTML)
Sprague,Wendy S.; Robbiani,Melissa; Avery,Paul R.; O'Halloran,Kevin P.; Hoover,Edward A.
Journal of General Virology 89(3): 709-715
Publication date: 2008
Resolution of de novo
HIV production and trafficking in immature dendritic cells (abstract) (HTML)
Turville,Stuart G.; Aravantinou,Meropi; Stoessel,Hella; Romani,Nikolaus; Robbiani,Melissa
Nature Methods 5(1): 75-85
Publication date: 2008
Current concepts of HIV transmission (abstract) (HTML)
Morrow,Gavin; Vachot,Laurence; Vagenas,Panagiotis; Robbiani,Melissa
Current HIV/AIDS Reports 4(1): 29-35
Publication date: 2007
Lymphocyte-dendritic cell interactions and mucosal acquisition of SIV/HIV infection (abstract) (HTML)
Turville,Stuart G.; Peretti,Silvia; Pope,Melissa
Current Opinion in HIV and AIDS 1(1): 3-9
Publication date: 2006
Slamming the door on unwanted guests: Why preemptive strikes at the mucosa may be the best strategy against HIV (abstract) (PDF)
Trapp,Susanna; Turville,Stuart G.; Robbiani,Melissa
Journal of Leukocyte Biology 80(5): 1076-1083
Publication date: 2006
Culture and comparison of feline myeloid dendritic cells vs. macrophages (abstract) (HTML)
Sprague,Wendy S.; Pope,Melissa; Hoover,Edward A.
Journal of Comparative Pathology 133(2-3): 136-145
Publication date: 2005
Elimination of retroviral infectivity by N-ethylmaleimide with preservation of functional envelope glycoproteins (abstract) (HTML)
Morcock,David R.; Thomas,James A.; Gagliardi,Tracy D.; Gorelick,Robert J.; Roser,J.David; Chertova,Elena N.; Bess Jr.,Julian W.; Ott,David E.; Sattentau,Quentin J.; Frank,Ines; Pope,Melissa; Lifson,Jeffrey D.; Henderson,Louis E.; Crise,Bruce J.
Journal of Virology 79(3): 1533-1542
Publication date: 2005
Immunomodulatory effects of HSV-2 infection on immature macaque dendritic cells modify innate and adaptive responses (abstract) (PDF) (HTML)
Peretti,Silvia; Shaw,Andrew; Blanchard,James; Bohm,Rudolf; Morrow,Gavin; Lifson,Jeffrey D.; Gettie,Agegnehu; Pope,Melissa
Blood 106(4): 1305-1313
Publication date: 2005
Blockade of attachment and fusion receptors inhibits HIV-1 infection of human cervical tissue (abstract) (PDF) (HTML)
Hu,Qinxue; Frank,Ines; Williams,Vennansha G.; Santos,John J.; Watts,Patricia; Griffin,George E.; Moore,John P.; Pope,Melissa; Shattock,Robin J.
Journal of Experimental Medicine 199(8): 1065-1075
Publication date: 2004
Immunodeficiency virus uptake, turnover, and 2-phase transfer in human dendritic cells (abstract) (PDF) (HTML)
Turville,Stuart G.; Santos,John J.; Frank,Ines; Cameron,Paul U.; Wilkinson,John; Miranda-Saksena,Monica; Dable,Joanne; Stoessel,Hella; Romani,Nikolaus; Piatak Jr.,Michael; Lifson,Jeffrey D.; Pope,Melissa; Cunningham,Anthony L.
Blood 103(6): 2170-2179
Publication date: 2004
Entry inhibitors SCH-C, RANTES, and T-20 block HIV type 1 replication in multiple cell types (abstract) (HTML)
Ketas,Thomas J.; Klasse,Per Johan; Spenlehauer,Catherine; Nesin,Mirjana; Frank,Ines; Pope,Melissa; Strizki,Julie M.; Reyes,Gregory R.; Baroudy,Bahige M.; Moore,John P.
AIDS Research and Human Retroviruses 19(3): 177-186
Publication date: 2003
Human immunodeficiency virus type 1 attachment, coreceptor, and fusion inhibitors are active against both direct and trans infection of primary cells (abstract) (PDF) (HTML)
Ketas,Thomas J.; Frank,Ines; Klasse,Per Johan; Sullivan,Brian M.; Gardener,Jason P.; Spenlehauer,Catherine; Nesin,Mirjana; Olson,William C.; Moore,John P.; Pope,Melissa
Journal of Virology 77(4): 2762-2767
Publication date: 2003
Immunodeficiency virus exploitation of dendritic cells in the early steps of infection (abstract) (PDF) (HTML)
Teleshova,Natalia; Frank,Ines; Pope,Melissa
Journal of Leukocyte Biology 74(5): 683-690
Publication date: 2003
Presentation of exogenous whole inactivated simian immunodeficiency virus by mature dendritic cells induces CD4+ and CD8+ T-cell responses (abstract) (HTML)
Frank,Ines; Santos,John J.; Mehlhop,Erin; Villamide-Herrera,Loreley; Santisteban,Christine; Gettie,Agegnehu; Ignatius,Ralf; Lifson,Jeffrey D.; Pope,Melissa
Journal of Acquired Immune Deficiency Syndromes 34(1): 7-19
Publication date: 2003
Prevention of virus transmission to macaque monkeys by a vaginally applied monoclonal antibody to HIV-1 gp120 (abstract) (HTML)
Veazey,Ronald S.; Shattock,Robin J.; Pope,Melissa; Kirijan,J.Christian; Jones,Jennifer; Hu,Qinxue; Ketas,Thomas J.; Marx,Preston A.; Klasse,Per Johan; Burton,Dennis R.; Moore,John P.
Nature Medicine 9(3): 343-346
Publication date: 2003
Transmission, acute HIV-1 infection and the quest for strategies to prevent infection (abstract) (HTML)
Pope,Melissa; Haase,Ashley T.
Nature Medicine 9(7): 847-852
Publication date: 2003
Endogenously expressed nef uncouples cytokine and chemokine production from membrane phenotypic maturation in dendritic cells (abstract) (PDF) (HTML)
Messmer,Davorka; Jacque,Jean-Marc; Santisteban,Christine; Bristow,Cynthia L.; Han,Seol-Young; Villamide-Herrera,Loreley; Mehlhop,Erin; Marx,Preston A.; Steinman,Ralph M.; Gettie,Agegnehu; Pope,Melissa
Journal of Immunology 169(8): 4172-4182
Publication date: 2002
Increased macrophage infection upon subcutaneous inoculation of rhesus macaques with simian immunodeficiency virus-loaded dendritic cells or T cells but not with cell-free virus (abstract) (PDF) (HTML)
Ignatius,Ralf; Tenner-Racz,Klara; Messmer,Davorka; Gettie,Agegnehu; Blanchard,James; Luckay,Amara; Russo,Christine; Smith,Stephen; Marx,Preston A.; Steinman,Ralph M.; Racz,Paul; Pope,Melissa
Journal of Virology 76(19): 9787-9797
Publication date: 2002
Infectious and whole inactivated simian immunodeficiency viruses interact similarly with primate dendritic cells (DCs): Differential intracellular fate of virions in mature and immature DCs (abstract) (PDF)
Frank,Ines; Piatak Jr.,Michael; Stoessel,Hella; Romani,Nikolaus; Bonnyay,David; Lifson,Jeffrey D.; Pope,Melissa
Journal of Virology 76(6): 2936-2951
Publication date: 2002
Rhesus macaque dendritic cells efficiently transmit primate lentiviruses independently of DC-SIGN (abstract) (PDF)
Wu,Li; Bashirova,Arman A.; Martin,Thomas D.; Villamide-Herrera,Loreley; Mehlhop,Erin; Chertov,Andrei O.; Unutmaz,Derya; Pope,Melissa; Carrington,Mary; KewalRamani,Vineet N.
Proceedings of the National Academy of Sciences of the United States of America 99(3): 1568-1573
Publication date: 2002
The enigma of dendritic cell-immunodeficiency virus interplay (abstract) (HTML)
Frank,Ines; Pope,Melissa
Current Molecular Medicine 2(3): 229-248
Publication date: 2002
Project Stats
Location: United States
Program(s):
HIV and AIDS
Topic(s):
HIV biomedical research
Duration: 1/2005 - ongoing
Population Council researchers:
Meropi Aravantinou
Nina Derby
Ines Frank
Joselin Galvez
Jessica Kenney
Elena Martinelli
Melissa Robbiani
Loreley Villamide-Herrera
Non-Council collaborators:
Agegnehu Gettie (Aaron Diamond AIDS Research Center)
Andrei Konradi (Elan Pharmaceuticals)
Andres Salazar (Oncovir)
James Arthos (US National Institutes of Health)
James Blanchard (Tulane National Primate Research Center)
Jeffrey Lifson (National Cancer Institute)
Julian Bess (National Cancer Institute)
Michael Piatak (National Cancer Institute)
Donors:
US National Institutes of Health
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