A mouse model for HIV-1 entry

Creators: Pietzsch, John; Gruell, Henning; Bournazos, Stylianos; Donovan, Bridget M.; Klein, Florian; Diskin, Ron; Seaman, Michael S.; Bjorkman, Pamela J.; Ravetch, Jeffrey V.; Ploss, Alexander; Nussenzweig, Michel C.

Abstract

Passive transfer of neutralizing antibodies against HIV-1 can prevent infection in macaques and seems to delay HIV-1 rebound in humans. Anti-HIV antibodies are therefore of great interest for vaccine design. However, the basis for their in vivo activity has been difficult to evaluate systematically because of a paucity of small animal models for HIV infection. Here we report a genetically humanized mouse model that incorporates a luciferase reporter for rapid quantitation of HIV entry. An antibody's ability to block viral entry in this in vivo model is a function of its bioavailability, direct neutralizing activity, and effector functions.

Additional Information

© 2012 National Academy of Sciences. Contributed by Michel C. Nussenzweig, August 2, 2012 (sent for review July 23, 2012). Published online before print September 10, 2012. We thank Johannes F. Scheid for providing the antibody plasmids of 3BNC60, 3BNC117, 1-74, and 1-79; Alexander Abadir, Kai-Hui Yao, Caroline Eden, and Marcus Dorner for technical assistance; David Bosque and Rachael Labitt for help with mouse colonies; Joseph Sodroski for providing pSVIIIenvYU-2 plasmid; and members of the M.C.N. laboratory for helpful discussions. The following reagents were obtained through the AIDS Research and Reference Reagent Program, Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH): pT4B from Richard Axel and pc.CCR-5 from Nathaniel Landau. This work was supported by grants from the Bill and Melinda Gates Foundation Collaboration for AIDS Vaccine Discovery (to M.S.S., P.J.B., J.V.R., and M.C.N.); and NIH Grant AI081677, "Novel Approaches to Vaccine Design" (to J.V.R. and M.C.N.). H.G. was supported by The German National Academic Foundation. F.K. was supported by German Research Foundation Grant KL 2389/1-1. A.P. is a recipient of the Astella Young Investigator Award of the Infectious Disease Society of America and of the Liver Scholar Award from the American Liver Foundation. P.J.B. and M.C.N. are Howard Hughes Medical Institute Investigators. Author contributions: J.P. and M.C.N. designed research; J.P., H.G., S.B., F.K., and M.S.S. performed research; J.P., H.G., S.B., B.M.D., R.D., P.J.B., J.V.R., and A.P. contributed new reagents/analytic tools; J.P., H.G., S.B., F.K., M.S.S., and M.C.N. analyzed data; and J.P. and M.C.N. wrote the paper.

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Published - PNAS-2012-Pietzsch-15859-64.pdf

Supplemental Material - pnas.201213409SI.pdf

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