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AIDS Res Hum Retroviruses. 2010 Jun;26(6):717-23. doi: 10.1089/aid.2009.0254.

Structural conservation predominates over sequence variability in the crown of HIV type 1's V3 loop.

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Department of Pharmacology, New York University School of Medicine (NYUSoM), New York, New York 10016, USA.


The diversity of HIV-1 is a confounding problem for vaccine design, as the human immune response appears to favor poor or strain-specific responses to any given HIV-1 virus strain. A significant portion of this diversity is manifested as sequence variability in the loops of HIV-1's surface envelope glycoprotein. Here we show that the most variable sequence positions in the third variable (V3) loop crown cluster to a small zone on the surface of one face of the V3 loop ss-hairpin conformation. These results provide a novel visualization of the gp120 V3 loop, specifically demonstrating a surprising preponderance of conserved three-dimensional structure in a highly sequence-variable region. From a structural point of view, there appears to be less diversity in this region of the HIV-1 "principle neutralizing domain" than previously appreciated.

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