Improvements and Limitations of Humanized Mouse Models for HIV Research: NIH/NIAID "Meet the Experts" 2015 Workshop Summary

doi:10.1089/AID.2015.0258

. 2016 Feb;32(2):109-19.

doi: 10.1089/AID.2015.0258.

Improvements and Limitations of Humanized Mouse Models for HIV Research: NIH/NIAID "Meet the Experts" 2015 Workshop Summary

Ramesh Akkina¹, Atef Allam^{2

3}, Alejandro B Balazs⁴, Joel N Blankson⁵, John C Burnett⁶, Sofia Casares⁷, J Victor Garcia⁸, Kim J Hasenkrug⁹, Fatah Kashanchi¹⁰, Scott G Kitchen¹¹, Florian Klein^{12

13}, Priti Kumar¹⁴, Andrew D Luster¹⁵, Larisa Y Poluektova¹⁶, Mangala Rao³, Brigitte E Sanders-Beer¹⁷, Leonard D Shultz¹⁸, Jerome A Zack¹¹

Affiliations

¹ 1 Department of Microbiology, Immunology and Pathology, Colorado State University , Fort Collins, Colorado.
² 2 Henry M. Jackson Foundation for the Advancement of Military Medicine , Silver Spring, Maryland.
³ 3 U.S. Military HIV Research Program, Walter Reed Army Institute of Research , Silver Spring, Maryland.
⁴ 4 The Ragon Institute of MGH , MIT & Harvard, Cambridge, Massachusetts.
⁵ 5 Department of Medicine, Center for AIDS Research, Johns Hopkins University School of Medicine , Baltimore, Maryland.
⁶ 6 Department of Molecular and Cellular Biology, Beckman Research Institute of City of Hope , Duarte, California.
⁷ 7 U.S. Military Malaria Vaccine Program, Naval Medical Research Center , Silver Spring, Maryland.
⁸ 8 Division of Infectious Diseases, Department of Medicine, UNC Center for AIDS Research, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina.
⁹ 9 Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories , NIAID, NIH, Hamilton, Montana.
¹⁰ 10 School of Systems Biology, National Center for Biodefense and Infectious Diseases, George Mason University , Manassas, Virginia.
¹¹ 11 Departments of Medicine and Microbiology, Immunology and Molecular Genetics, UCLA AIDS Institute , Los Angeles, California.
¹² 12 First Department of Internal Medicine, University Hospital of Cologne , Cologne, Germany .
¹³ 13 Center for Molecular Medicine Cologne (CMMC), University of Cologne , Cologne, Germany .
¹⁴ 14 School of Medicine, Infectious Diseases/Internal Medicine, Yale University , New Haven, Connecticut.
¹⁵ 15 Center for Immunology and Inflammatory Diseases , Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
¹⁶ 16 Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center , Omaha, Nebraska.
¹⁷ 17 National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, Maryland.
¹⁸ 18 The Jackson Laboratory , Bar Harbor, Maine.

PMID: 26670361
PMCID: PMC4761823
DOI: 10.1089/AID.2015.0258

Improvements and Limitations of Humanized Mouse Models for HIV Research: NIH/NIAID "Meet the Experts" 2015 Workshop Summary

Ramesh Akkina et al. AIDS Res Hum Retroviruses. 2016 Feb.

. 2016 Feb;32(2):109-19.

doi: 10.1089/AID.2015.0258.

Authors

Affiliations

¹ 1 Department of Microbiology, Immunology and Pathology, Colorado State University , Fort Collins, Colorado.
² 2 Henry M. Jackson Foundation for the Advancement of Military Medicine , Silver Spring, Maryland.
³ 3 U.S. Military HIV Research Program, Walter Reed Army Institute of Research , Silver Spring, Maryland.
⁴ 4 The Ragon Institute of MGH , MIT & Harvard, Cambridge, Massachusetts.
⁵ 5 Department of Medicine, Center for AIDS Research, Johns Hopkins University School of Medicine , Baltimore, Maryland.
⁶ 6 Department of Molecular and Cellular Biology, Beckman Research Institute of City of Hope , Duarte, California.
⁷ 7 U.S. Military Malaria Vaccine Program, Naval Medical Research Center , Silver Spring, Maryland.
⁸ 8 Division of Infectious Diseases, Department of Medicine, UNC Center for AIDS Research, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina.
⁹ 9 Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories , NIAID, NIH, Hamilton, Montana.
¹⁰ 10 School of Systems Biology, National Center for Biodefense and Infectious Diseases, George Mason University , Manassas, Virginia.
¹¹ 11 Departments of Medicine and Microbiology, Immunology and Molecular Genetics, UCLA AIDS Institute , Los Angeles, California.
¹² 12 First Department of Internal Medicine, University Hospital of Cologne , Cologne, Germany .
¹³ 13 Center for Molecular Medicine Cologne (CMMC), University of Cologne , Cologne, Germany .
¹⁴ 14 School of Medicine, Infectious Diseases/Internal Medicine, Yale University , New Haven, Connecticut.
¹⁵ 15 Center for Immunology and Inflammatory Diseases , Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
¹⁶ 16 Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center , Omaha, Nebraska.
¹⁷ 17 National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, Maryland.
¹⁸ 18 The Jackson Laboratory , Bar Harbor, Maine.

PMID: 26670361
PMCID: PMC4761823
DOI: 10.1089/AID.2015.0258

Abstract

The number of humanized mouse models for the human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) and other infectious diseases has expanded rapidly over the past 8 years. Highly immunodeficient mouse strains, such as NOD/SCID/gamma chain(null) (NSG, NOG), support better human hematopoietic cell engraftment. Another improvement is the derivation of highly immunodeficient mice, transgenic with human leukocyte antigens (HLAs) and cytokines that supported development of HLA-restricted human T cells and heightened human myeloid cell engraftment. Humanized mice are also used to study the HIV reservoir using new imaging techniques. Despite these advances, there are still limitations in HIV immune responses and deficits in lymphoid structures in these models in addition to xenogeneic graft-versus-host responses. To understand and disseminate the improvements and limitations of humanized mouse models to the scientific community, the NIH sponsored and convened a meeting on April 15, 2015 to discuss the state of knowledge concerning these questions and best practices for selecting a humanized mouse model for a particular scientific investigation. This report summarizes the findings of the NIH meeting.

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References

1. Duyne RV, Narayanan A K-H.all K, Saifuddin M, Shultz L, Kashanchi F: Humanized mouse models of HIV-1 latency. Curr HIV Res 2011;9:595–605 - PubMed
1. Brehm MA, Jouvet N, Greiner DL, Shultz LD: Humanized mice for the study of infectious diseases. Curr Opin Immunol 2013;25:428–435 - PMC - PubMed
1. McCune JM, Namikawa R, Kaneshima H, Shultz LD, Lieberman M, Weissman IL: The SCID-hu mouse: Murine model for the analysis of human hematolymphoid differentiation and function. Science 1988;241:1632–1639 - PubMed
1. McCune JM, Shultz LD: Humanized mice as models for human disease. In: Humanized Mice for HIV Research (Poluektove LY, Garcia JV, Koyanagi Y, Manz MG, Tager AM, eds.) Springer-Verlag, New York, 2014, pp. 15–24
1. Namikawa R, Kaneshima H, Lieberman M, Weissman IL, McCune JM: Infection of the SCID-hu mouse by HIV-1. Science 1988;242:1684–1686 - PubMed

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[1] Duyne RV, Narayanan A K-H.all K, Saifuddin M, Shultz L, Kashanchi F: Humanized mouse models of HIV-1 latency. Curr HIV Res 2011;9:595–605 - PubMed

[2] Duyne RV, Narayanan A K-H.all K, Saifuddin M, Shultz L, Kashanchi F: Humanized mouse models of HIV-1 latency. Curr HIV Res 2011;9:595–605 - PubMed

[3] Brehm MA, Jouvet N, Greiner DL, Shultz LD: Humanized mice for the study of infectious diseases. Curr Opin Immunol 2013;25:428–435 - PMC - PubMed

[4] Brehm MA, Jouvet N, Greiner DL, Shultz LD: Humanized mice for the study of infectious diseases. Curr Opin Immunol 2013;25:428–435 - PMC - PubMed

[5] McCune JM, Namikawa R, Kaneshima H, Shultz LD, Lieberman M, Weissman IL: The SCID-hu mouse: Murine model for the analysis of human hematolymphoid differentiation and function. Science 1988;241:1632–1639 - PubMed

[6] McCune JM, Namikawa R, Kaneshima H, Shultz LD, Lieberman M, Weissman IL: The SCID-hu mouse: Murine model for the analysis of human hematolymphoid differentiation and function. Science 1988;241:1632–1639 - PubMed

[7] McCune JM, Shultz LD: Humanized mice as models for human disease. In: Humanized Mice for HIV Research (Poluektove LY, Garcia JV, Koyanagi Y, Manz MG, Tager AM, eds.) Springer-Verlag, New York, 2014, pp. 15–24

[8] McCune JM, Shultz LD: Humanized mice as models for human disease. In: Humanized Mice for HIV Research (Poluektove LY, Garcia JV, Koyanagi Y, Manz MG, Tager AM, eds.) Springer-Verlag, New York, 2014, pp. 15–24

[9] Namikawa R, Kaneshima H, Lieberman M, Weissman IL, McCune JM: Infection of the SCID-hu mouse by HIV-1. Science 1988;242:1684–1686 - PubMed

[10] Namikawa R, Kaneshima H, Lieberman M, Weissman IL, McCune JM: Infection of the SCID-hu mouse by HIV-1. Science 1988;242:1684–1686 - PubMed

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Improvements and Limitations of Humanized Mouse Models for HIV Research: NIH/NIAID "Meet the Experts" 2015 Workshop Summary

Affiliations

Improvements and Limitations of Humanized Mouse Models for HIV Research: NIH/NIAID "Meet the Experts" 2015 Workshop Summary

Authors

Affiliations

Abstract

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References

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