title: Association between HIV-1 coreceptor usage and resistance to broadly neutralizing antibodies.
abstract: BACKGROUND
  Recently discovered broadly neutralizing antibodies have revitalized hopes of developing a universal vaccine against HIV-1. Mainly responsible for new infections are variants only using CCR5 for cell entry, whereas CXCR4-using variants can become dominant in later infection stages.
  
  
  METHODS
  We performed a statistical analysis on two different previously published data sets. The first data set was a panel of 199 diverse HIV-1 isolates for which IC50 neutralization titers were determined for the broadly neutralizing antibodies VRC01, VRC-PG04, PG9, and PG16. The second data set contained env sequences of viral variants extracted from HIV-1-infected humanized mice treated with the antibody PGT128 and from untreated control mice.
  
  
  RESULTS
  For the panel of 199 diverse HIV-1 isolates, we found a statistically significant association between viral resistance to PG9 and PG16 and CXCR4 coreceptor usage (P = 0.0011 and P = 0.0010, respectively). Our analysis of viral variants from HIV-1-infected humanized mice under treatment with the broadly neutralizing antibody PGT128 indicated that certain antibodies might drive a viral population toward developing CXCR4 coreceptor usage capability (P = 0.0011 for the comparison between PGT128 and control measurement).
  
  
  CONCLUSIONS
  These analyses highlight the importance of accounting for a possible coreceptor usage bias pertaining to the effectiveness of an HIV vaccine and to passive antibody transfer as therapeutic approach.
authors: *Department of Computational Biology and Applied Algorithmics, Max Planck Institute for Informatics, Saarbrücken, Germany; and †MVZ Medizinisches Infektiologiezentrum Berlin, Berlin, Germany.
authors: Nico
authors: N
authors: Pfeifer
authors: Hauke
authors: H
authors: Walter
authors: Thomas
authors: T
authors: Lengauer
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology*; D015483:HIV Antibodies / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology* / Q000821:virology*; D015497:HIV-1 / Q000276:immunology* / Q000502:physiology; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D016513:Mice, SCID; D009500:Neutralization Tests; D015728:Receptors, HIV / Q000032:analysis*; D053586:Virus Internalization
chemical_list: D057134:Antibodies, Neutralizing; D015483:HIV Antibodies; D015728:Receptors, HIV