Population Council Research that makes a difference

Robbiani Laboratory

Researchers in Melissa Robbiani's laboratory at the Center for Biomedical Research in New York City perform studies to understand the mechanism of sexual transmission of HIV—with particular focus on the role of dendritic cells—and examine ways to prevent HIV spread. Dendritic cells are a type of white blood cell that is critical in orchestrating innate and adaptive immune function. HIV manages to exploit dendritic cells to facilitate infection, instead of protective immunity.

Studies involve extensive in vitro analyses and in vivo translational studies. Delineating exactly how dendritic cells drive HIV infection across the body surfaces is critical to advancing preventive strategies, including:

  • antiviral microbicides to directly prevent infections and
  • immunostimulatory approaches to boost innate and adaptive immunity elicited by natural infection or vaccines.

The impact of other common pathogens (e.g., herpes simplex virus and Candida albicans) on these events also is being researched.


 

Challenges in preventing HIV infection

Challenges in preventing HIV infection: After breaching the epithelial barrier, HIV gains access to white bloods cells (dendritic cells [DCs] and T cells) that are able to amplify virus growth. DCs can capture and internalize HIV or they can become infected by HIV. Such captured viruses and newly produced viruses are efficiently spread from DCs to CD4 T cells, thereby rapidly amplifying HIV growth locally and distally in the lymphoid tissues after the virus-bearing DCs migrate to the draining lymph nodes. Antiviral microbicides or immune responses induced by vaccines need to block these events and/or inactivate the virus entering the body in order to limit infection. Microbicides might also act by preventing the initial entry of HIV into the body. Microbicides must not perturb the normal flora. In addition, if a microbicide has broader activity against other sexually transmitted infections (STIs) that can exacerbate HIV transmission, it will further help limit HIV spread. Illustration: Evan Read/Population Council.



Projects

    • Impact of Antiretroviral Therapy on Mucosal Immunity (more)
      Council researchers are investigating the potential influence of long-term antiretroviral therapy on oral immune function.
      (1/2005 - 12/2012)
      United States
    • In Vitro and In Vivo Testing of Microbicides (more)
      Council research is advancing microbicide strategies to prevent dendritic cell–driven infection of HIV across the body surfaces.
      (1/2005 - ongoing)
      United States
    • A Novel DARPins Strategy for Combating HIV (more)
      Council researchers identify the optimal cocktail of CD4-specific DARPins to limit HIV replication in vitro and provide the first tests of this novel antiviral strategy in vivo.
      (7/2008 - 6/2014)
      Switzerland, United States
    • Transmission of Immunodeficiency Viruses: Dendritic Cells and Innate and Adaptive Immune Responses (more)
      Understanding how human immunodeficiency virus (HIV) is transmitted during sexual intercourse and how co-pathogens impact HIV spread is a focus of Council research.
      (1/2005 - ongoing)
      United States

Laboratory members

    • Melissa Robbiani (senior scientist/director of biomedical HIV research)
    • Loreley Villamide-Herrera (biomedical program manager)
    • Joselin Galvez (biomedical program coordinator)
    • Elena Martinelli (scientist)
    • Nina Derby, Mayla Hsu (senior research investigators)
    • Ines Frank, Pavel Pugach (research investigators)
    • Filippo Veglia (postdoctoral fellow)
    • Jessica Kenney (laboratory manager)
    • Meropi Aravantinou (senior research technician)

External collaborators

    • James Arthos (US National Institutes of Health, Bethesda, Maryland)
    • Julian Bess, Jeffrey Lifson, Michael Piatak (SAIC/National Cancer Institute, Frederick, Maryland)
    • James Blanchard (Tulane National Primate Research Center, Covington, Louisiana)
    • Agegnehu Gettie (Aaron Diamond AIDS Research Center, New York, New York)
    • Andrei Konradi (Elan Pharmaceuticals, South San Francisco, California)
    • Andres Salazar (Oncovir, Inc., Washington, DC)
    • Alexandra Trkola (University of Zurich, Institute of Medical Virology, Switzerland)

Selected resources

Search our publications database for more resources related to the Robbiani laboratory

Simian immunodeficiency virus interactions with macaque dendritic cells
Teleshova,Natalia; Derby,Nina R.; Martinelli,Elena; Pugach,Pavel; Calenda,Giulia; Robbiani,Melissa
In "HIV interactions with dendritic cells: Infection and immunity," from Wu,L. and Schwartz,O. (eds.), Topics in HIV and AIDS Research. New York: Springer
Publication date: Forthcoming

Non-specific microbicide development: Then and now (abstract)
Romano,Joseph W.; Robbiani,Melissa; Doncel,Gustavo F.; Moench,Thomas
Current HIV Resarch 10(1): 9–18
Publication date: 2012

Zinc acetate/carrageenan gels exhibit potent activity in vivo against high-dose HSV-2 vaginal and rectal challenge  (abstract
Fernandez-Romero,Jose A.; Abraham,Ciby J.; Rodriguez,Aixa; Kizima,Larisa; Jean-Pierre,Ninochka; Menon,Radhika; Begay,Othell; Seidor,Samantha; Ford,Brian E.; Gil,Pedro I.; Peters,Jennifer; Katz,David; Robbiani,Melissa; Zydowsky,Thomas M.
Antimicrobial Agents and Chemotherapy 56(1): 358–368
Publication date: 2012

An antiretroviral/zinc combination gel provides 24 hours of complete protection against vaginal SHIV infection in macaques  (abstract) (PDF
Kenney,Jessica; Aravantinou,Meropi; Singer,Rachel; Hsu,Mayla; Rodriguez,Aixa; Kizima,Larisa; Abraham,Ciby J.; Menon,Radhika; Seidor,Samantha; Chudolij,Anne; Gettie,Agegnehu; Blanchard,James; Lifson,Jeffrey D.; Piatak Jr.,Michael; Fernandez-Romero,Jose A.; Zydowsky,Thomas M.; Robbiani,Melissa
PLoS ONE 6(1): E15835-
Publication date: 2011

Attachment and fusion inhibitors potently prevent DC-driven infection
Frank,Ines; Robbiani, Melissa
Journal of Acquired Immune Deficiency Syndromes 56(3):204–212.
Publication date: 2011

HSV-2 infection of dendritic cells amplifies a highly susceptible HIV-1 cell target  (abstract) (PDF
Martinelli,Elena; Tharinger,Hugo; Frank,Ines; Arthos,James; Piatak Jr.,Michael; Lifson,Jeffrey D.; Blanchard,James; Gettie,Agegnehu; Robbiani,Melissa
PLoS Pathogens 7(6): e1002109. doi:10.1371/journal.ppat.1002109-
Publication date: 2011

The nonnucleoside reverse transcriptase inhibitor MIV-150 in carrageenan gel prevents rectal transmission of simian/human immunodeficiency virus infection in macaques  (abstract
Singer,Rachel; Derby,Nina R.; Rodriguez,Aixa; Kizima,Larisa; Kenney,Jessica; Aravantinou,Meropi; Chudolij,Anne; Gettie,Agegnehu; Blanchard,James; Lifson,Jeffrey D.; Piatak Jr.,Michael; Fernandez-Romero,Jose A.; Zydowsky,Thomas M.; Robbiani,Melissa
Journal of Virology 85(11): 5504-5512
Publication date: 2011

In vivo binding and retention of CD4-Specific DARPin 57.2 in macaques  (abstract) (PDF
Pugach,Pavel; Krarup,Anders; Gettie,Agegnehu; Kuroda,Marcelo; Blanchard,James; Piatak Jr.,Michael; Lifson,Jeffrey D.; Trkola,Alexandra; Robbiani,Melissa
PLoS ONE 5(8): e12455 (1)-e12455 (9)
Publication date: 2010

A tonsillar polyICLC/AT-2 SIV therapeutic vaccine maintains low viremia following antiretroviral therapy cessation  (abstract) (PDF
Vagenas,Panagiotis; Aravantinou,Meropi; Williams,Vennansha G.; Jasny,Edith; Piatak Jr.,Michael; Lifson,Jeffrey D.; Salazar,Andres M.; Blanchard,James; Gettie,Agegnehu; Robbiani,Melissa
PLoS ONE 5(9): e12891 (1)-e12891 (13)
Publication date: 2010

A macaque model to study vaginal HSV-2/immunodeficiency virus co-infection and the impact of HSV-2 on microbicide efficacy  (abstract) (HTML
Crostarosa,Federica; Aravantinou,Meropi; Akpogheneta,Onome J.; Jasny,Edith; Shaw,Andrew; Kenney,Jessica; Piatak Jr.,Michael; Lifson,Jeffrey D.; Teitelbaum,Aaron; Hu,Lieyu; Chudolij,Anne; Zydowsky,Thomas M.; Blanchard,James; Gettie,Agegnehu; Robbiani,Melissa
PLoS ONE 4(11): e8060 (1)-e8060 (14)
Publication date: 2009

Double-stranded RNA analog poly(I:C) inhibits human immunodeficiency virus amplification in dendritic cells via type I interferon-mediated activation of APOBEC3G (abstract)
Trapp, Susanna; Derby, Nina R.; Singer, Rachel; Shaw, Andrew; Williams, Vennansha G.; Turville, Stuart G.; Bess Jr., Julian W.; Lifson, Jeffrey D.; Robbiani, Melissa
Journal of Virology 83(2): 884-895
Publication date: 2009

A fusion inhibitor prevents spread of immunodeficiency viruses, but not activation of virus-specific T cells, by dendritic cells
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

Candida albicans-induced DC activation reduces HIV amplification by DCs while increasing DC-to-T-cell spread of HIV (abstract)
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

CD4-specific Designed Ankyrin Repeat Proteins are novel potent HIV entry inhibitors with unique characteristics (offsite HTML)
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 (offsite HTML)
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

Resolution of de novo HIV production and trafficking in immature dendritic cells (abstract)
Turville, Stuart G.; Aravantinou, Meropi; Stoessel, Hella; Romani, Nikolaus; Robbiani, Melissa
Nature Methods 5(1): 75-85
Publication Date: 2008

 

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