Abstract
Antibodies that can neutralize diverse HIV-1 strains develop in ~10–20% of HIV-1 infected individuals, and their elicitation is a goal of vaccine design. Such antibodies can also serve as therapeutics for those who have already been infected with the virus. Structural characterizations of broadly reactive antibodies in complex with the HIV-1 spike indicate that there are a limited number of sites of vulnerability on the spike. Analysis of their structures can help reveal commonalities that would be useful in vaccine design and provide insights on combinations of antibodies that can be used to minimize the incidence of viral resistance mutations. In this review, we give an update on recent structures determined of the spike in complex with broadly neutralizing antibodies in the context of all epitopes on the HIV-1 spike identified to date.
Highlights
We focus on broadly neutralizing antibodies (bnAbs) that have been more recently structurally characterized in complex with Env
HIV-1 mechanisms, bnAbs targeting a significant variants beendefense produced by some HIV-1 infected individuals, as well as number by mice orof viral variants have been produced by some infected to individuals, as well as by mice or other animals
IC50 = 0.055 μg/mL), it had reduced breadth with 38.1% neutralization of a 42-pseudovirus panel. As these bnAbs resembled binding to Env of human V1V2 and V3 glycan supersite bnAbs, their elicitation in rhesus macaques highlights the utility of using these animals for studying HIV-1 bnAb development
Summary
HIV-1 is a rapidly evolving pathogen, which has necessitated the use of antiretroviral therapies that use cocktails of drugs, to treat infected individuals while minimizing the development of resistance. Gp120 binding to CD4 leads to a large conformational change in which the trimer “opens” This involves a rearrangement of the V1V2 and V3 loops and formation of a bridging sheet [22,23]. The gp protein folds into a hairpin structure in which the two heptad repeats, HR1 and HR2, form a six-helix bundle, bringing the viral and host cell membranes into contact to complete fusion [25,26]. The α4 β7 integrin has been suggested to play an important role in HIV entry by interacting with the gp120 V2 loop of (green) subunits are shown with their variable loops, V1V2 (cyan), V3 (purple), and V5 (white) in different conformations as they go through the fusion process. Binding partners on the host are shown, α4β7 (red, navy), CD4 (blue), and the coreceptor (orange)
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