Molecular recognition of the native HIV-1 MPER revealed by STED microscopy of single virions
Visualization of the native MPER Env site on intact HIV virions through super-resolution STED microscopy. Contrary to previous assumptions, this site is accessible to neutralizing antibodies, whose functionality can be improved by strengthening their interaction with the viral membrane. Fabs and virions are labeled in orange and green colors, respectively
Carravilla P, Chojnacki J, Rujas E, Insausti S, Largo E, Waithe D, Apellaniz B, Sicard T, Julien JP, Eggeling C, Nieva JL.
Nat Commun 2019 Jan; 10: 78.
Antibodies against the Membrane-Proximal External Region (MPER) of the Env gp41 subunit neutralize HIV-1 with exceptional breadth and potency. Due to the lack of knowledge on the MPER native structure and accessibility, different and exclusive models have been proposed for the molecular mechanism of MPER recognition by broadly neutralizing antibodies. Here, accessibility of antibodies to the native Env MPER on single virions has been addressed through STED microscopy. STED imaging of fluorescently labeled Fabs reveals a common pattern of native Env recognition for HIV-1 antibodies targeting MPER or the surface subunit gp120. In the case of anti-MPER antibodies, the process evolves with extra contribution of interactions with the viral lipid membrane to binding specificity. Our data provide biophysical insights into the recognition of the potent and broadly neutralizing MPER epitope on HIV virions, and as such is of importance for the design of therapeutic interventions.
PubMed: 30622256. Doi: 10.1038/s41467-018-07962-9. Free PMC article
