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ARS Home » Northeast Area » Beltsville, Maryland (BHNRC) » Beltsville Human Nutrition Research Center » Diet, Genomics and Immunology Laboratory » Research » Publications at this Location » Publication #126988


item Ding, Jianping
item Smith, Allen
item Geisler, Sheila
item Arnold, Gail
item Arnold, Edward

Submitted to: Structure
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/2/2002
Publication Date: 7/1/2002
Citation: Ding, J., Smith, A.D., Geisler, S., Arnold, G., Arnold, E. 2002. Crystal structure of a human rhinovirus type 14 (hrv14): human immuno- deficiency virus type 1 (hiv-1) v3 loop chimeric virus that induces neutralizing antibodies against hiv-1.. Structure.

Interpretive Summary: Currently, there is not a useful vaccine for the treatment or prevention of AIDS. In an attempt to address this problem we have created designer "common cold" or rhinoviruses that present a specific region of the HIV important for entry of the virus to the cell on the surface of the human rhinovirus (HRV14). These new viruses are called chimeric rhinoviruses (HRV:HIV-1) because they are mostly rhinovirus but have a part of a protein that makes up HIV on its surface. Previously we have shown that these chimeric HRV14:HIV viruses can induce animals to make and can also bind antibodies that stop HIV from infecting cells in the laboratory. To gain a better understanding of what the chimeric virus looks like, a technique called X-ray crystallography was used to determine the three- dimensional structure of the HRV14:HIV chimera. In this way the piece of HIV that was transplanted onto the rhinovirus can be seen and a better understanding of how this region may act in HIV and affect the ability of the virus to infect different types of cells.

Technical Abstract: Background: With the goal of developing an AIDS vaccine component, we previously made a combinatorial library of common cold-causing rhinoviruses displaying a diverse set of conformations of the immunogenic HIV-1 gp120 V3 loop region. In this library, the V3 loop sequence, IGPGRAFYTTKN, was flanked by 0-3 randomized residues on each side and inserted between Ala 159 and Asn 160 of viral protein 2. A chimeric virus, designated MN-III-2, was selected using anti-V3 loop monoclonal antibodies. This virus was able to elicit the production of guinea pig antisera capable of neutralizing HIV-1. Results: The structure of the MN-III-2 chimeric virus has been solved and refined at 2.7 A resolution. The overall structure of MN-III-2 is similar to that of wild-type HRV14. The structure of the V3 loop insert is dominated by two type I b turns, the first consisting of residues GRAF and the second, residues TTKN. The V3 loop sequence of MN-III-2 adopts a different overall conformation from that seen in three Fab/peptide complexes. The major conformational difference is localized to the GR residues of the first type I b turn. However, the GPG and the RAF residues in the chimeric virus can be superimposed upon the corresponding segments in the Fab/peptide complexes. Conclusions: The results suggest that the V3 loop has inherent conformational flexibility and can adopt multiple conformations. The relatively conserved GPGRAF motif of the V3 loop appears to consist of two well defined structural modules that can alter their relative orientations, resulting in distinct V3 loop conformations.