Antigp41 antibodies fail to block early events of virological synapses but inhibit HIV spread between T cells

Marta Massanella, Isabel Puigdoménech, Cecilia Cabrera, Maria Teresa Fernandez-Figueras, Anne Aucher, Gerald Gaibelet, Denis Hudrisier, Elisabet García, Margarita Bofill, Bonaventura Clotet, Julià Blanco

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Abstract

Objective: Compared with cell-free viral infection, virological synapses increase HIV capture by target cells, viral infectivity and cytopathicity, and are believed to be less sensitive to antibody neutralization. We have evaluated the impact of antibodies against HIV envelope glycoproteins (gp120 and gp41) on cell-to-cell HIV transmission. Methods: We analyzed the role of trogocytosis in cell-to-cell HIV transmission and the inhibitory mechanisms of antigpl 20 antibody IgGbl 2 and antigp41 antibodies 4E10 and 2F5 using cocultures of IML4-3 or BaL-infected MOLT/CCR5 cells with primary CD4 T cells. Results: Analysis of early steps of HIV transmission in these cocultures showed that IgGbl 2, but not 4E10 and 2F5, inhibited the formation of virological synapses. Consequently, IgGb12 but not antigp41 antibodies blocked the transfer of HIV particles from infected to target cells and the trogocytic transfer of CD4 molecules from target to infected cells. Interestingly, trogocytic transfer of membranes was not detected in the HIV transmission direction. Furthermore, analysis of late events of HIV transmission showed that all neutralizing antibodies blocked productive infection of target cells, suggesting that HIV infection between T cells is transmitted by a neutralization-sensitive mechanism involving HIV budding from infected cells and capture by target cells. Conclusion: Despite mechanistic differences, antigpl 20 and antigp41 antibodies block infectious cell-to-cell HIV transmission. Our data suggest that eliciting high titers of neutralizing antibodies in vivo should be maintained as a main end of HIV vaccine design. © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins.
Original languageEnglish
Pages (from-to)183-188
JournalAIDS
Volume23
Issue number2
DOIs
Publication statusPublished - 14 Jan 2009

Keywords

  • Humoral response
  • Neutralization
  • Trogocytosis
  • Virological synapses

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    Massanella, M., Puigdoménech, I., Cabrera, C., Fernandez-Figueras, M. T., Aucher, A., Gaibelet, G., Hudrisier, D., García, E., Bofill, M., Clotet, B., & Blanco, J. (2009). Antigp41 antibodies fail to block early events of virological synapses but inhibit HIV spread between T cells. AIDS, 23(2), 183-188. https://doi.org/10.1097/QAD.0b013e32831ef1a3