Antigp41 antibodies fail to block early events of virological synapses but inhibit HIV spread between T cells.
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 antigp120 antibody IgGb12 and antigp41 antibodies 4E10 and 2F5 using cocultures of NL4-3 or BaL-infected MOLT/CCR5 cells with primary CD4 T cells.


RESULTS
Analysis of early steps of HIV transmission in these cocultures showed that IgGb12, 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.


CONCLUSIONS
Despite mechanistic differences, antigp120 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.
Massanella
Marta
M
Fundació irsiCaixa-HIVACAT, Institut de Recerca en Ciències de la Salut Germans Trias I Pujol (IGTP), Barcelona, Catalonia, Spain.
Puigdomènech
Isabel
I
Cabrera
Cecilia
C
Fernandez-Figueras
Maria Teresa
MT
Aucher
Anne
A
Gaibelet
Gerald
G
Hudrisier
Denis
D
García
Elisabet
E
Bofill
Margarita
M
Clotet
Bonaventura
B
Blanco
Julià
J
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology*; D002450:Cell Communication / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D004705:Endocytosis / Q000276:immunology; D015483:HIV Antibodies / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D015700:HIV Envelope Protein gp41 / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology / Q000502:physiology*; D006801:Humans; D054992:Immunological Synapses / Q000276:immunology; D053586:Virus Internalization
D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41