Viren sind schon ein gemeines Volk und das HI-Virus erst recht. Aber jetzt gibt es möglicherweise Hoffnung auf einen Impfstoff.
The AIDS virus evades the immune system because most of the proteins that cover the surface of the virus constantly change their structure [das HI-Virus hat eine hohe Mutationsrate]. But researchers have now identified a site that doesn't change, and shown how an antibody can bind to it. If the body could be stimulated to produce its own copies of this antibody before infection, then in theory, it would allow it to attack the otherwise elusive virus and prevent infection.
The discovery hinges on an HIV protein called gp120 [ein Bestandteil der Virushülle]. During infection, gp120 latches onto a protein found in the human immune system called CD4 [ein Oberflächenmarker von bestimmten T-Zellen, die das Virus befällt und in denen das Virus vermehrt wird]. Because this is an essential step in the virus's replication cycle, a key site within gp120 retains its conformation, unlike other HIV surface proteins.
Antikörper werden von B-Zellen produziert. Ein Antikörper ist jeweils spezifisch für ein ganz bestimmtes Epitop (einen Teilbereich eines Proteins) und bindet nur dies. Viruspartikel können durch gebundene Antikörper inaktiviert werden (d.h. sie können keine neuen Zellen mehr befallen) und zudem markiert sie der gebundene Antikörper für die Aufnahme durch Makrophagen ("Fresszellen"), wodurch das Virus zerstört wird.
The remarkable diversity, glycosylation and conformational flexibility of the human immunodeficiency virus type 1 (HIV-1) envelope (Env), including substantial rearrangement of the gp120 glycoprotein upon binding the CD4 receptor, allow it to evade antibody-mediated neutralization. Despite this complexity, the HIV-1 Env must retain conserved determinants that mediate CD4 binding. To evaluate how these determinants might provide opportunities for antibody recognition, we created variants of gp120 stabilized in the CD4-bound state, assessed binding of CD4 and of receptor-binding-site antibodies, and determined the structure at 2.3 Å resolution of the broadly neutralizing antibody b12 in complex with gp120. b12 binds to a conformationally invariant surface that overlaps a distinct subset of the CD4-binding site. This surface is involved in the metastable attachment of CD4, before the gp120 rearrangement required for stable engagement. A site of vulnerability, related to a functional requirement for efficient association with CD4, can therefore be targeted by antibody to neutralize HIV-1. QuelleAbb. 4: Structural definition of a conformationally invariant, antibody-accessible portion of the CD4-binding site.
The b12- and CD4-bound conformations of gp120 are shown in ribbon representation, after superposition of outer domains (red). A semitransparent molecular surface shows the contact surfaces of b12 (green) and CD4 (yellow). Subsets of these surfaces, corresponding to regions of conformational flexibility (for example, of the inner domain (grey) or bridging sheet (blue)), are delineated, as are regions of b12 contact outside of the conserved CD4-binding site. As can be seen, functional analysis serves to transcend the particulars of b12 binding, whereas antibody defines accessibility. Although we have formally shown only the b12 contact surface to be accessible in the context of a functional viral spike, the highly effective neutralization of D1D2-Igalphatp and the kinetics of its association with both core and OD1 variants of gp120 suggest that the CD4-binding surface on the outer domain is accessible.
Es ist mit Sicherheit zu früh, in Begeisterungsstürme auszubrechen, aber dies ist ein erster Hoffnungsschimmer.A vaccine could do this in several ways, says Kwong. It could be a protein or a string of DNA that gives the body information on how to produce b12. Or a part of the HIV gp120 protein could be used to stimulate the body to raise antibodies against it.
Some people infected with HIV have developed similar antibodies. But because they have already been exposed to the virus, it is too late to prevent permanent infection. So, such a vaccine would work only if given before infection.
The question, says Kwong, is whether a drug can be developed that stimulates antibody production in someone who has never encountered the virus. The researchers now plan animal tests to see whether high levels of the antibody can be achieved. Quelle: news@nature
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