Perspectives on Non-BLT Humanized Mouse Models for Studying HIV Pathogenesis and Therapy

A variety of humanized mice, which are reconstituted only with human hematopoietic stem cells (HSC) or with fetal thymus and HSCs, have been developed and widely utilized as in vivo animal models of HIV-1 infection. The models represent some aspects of HIV-mediated pathogenesis in humans and are use...

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Published inViruses Vol. 13; no. 5; p. 776
Main Authors Terahara, Kazutaka, Iwabuchi, Ryutaro, Tsunetsugu-Yokota, Yasuko
Format Journal Article
LanguageEnglish
Published Switzerland MDPI AG 28.04.2021
MDPI
Subjects
Animal models
Animals
Antigens
antiretroviral agents
Bone Marrow
Cytokines
Disease Models, Animal
experimental design
Fetuses
Genotype & phenotype
Hematopoietic Stem Cell Transplantation
Hematopoietic Stem Cells
HIV
HIV infection
HIV infections
HIV Infections - drug therapy
HIV Infections - physiopathology
HIV-1 - drug effects
HIV-1 - pathogenicity
HIV-1 - physiology
Human immunodeficiency virus
humanized mice
Humans
Immune response
immunological features
Immunology
Infections
Liver
Lymphatic system
Lymphocytes
Lymphoid tissue
Mice
Mice, Inbred Strains
Mice, Transgenic
non-BLT
Pathogenesis
Review
Rodents
Spleen
Stem cell transplantation
Stem cells
therapeutics
therapy
Thymus Gland
United States > US
non-BLT
pathogenesis
HIV infection
therapy
immunological features
humanized mice
Online AccessGet full text
ISSN1999-4915
1999-4915
DOI10.3390/v13050776

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Abstract A variety of humanized mice, which are reconstituted only with human hematopoietic stem cells (HSC) or with fetal thymus and HSCs, have been developed and widely utilized as in vivo animal models of HIV-1 infection. The models represent some aspects of HIV-mediated pathogenesis in humans and are useful for the evaluation of therapeutic regimens. However, there are several limitations in these models, including their incomplete immune responses and poor distribution of human cells to the secondary lymphoid tissues. These limitations are common in many humanized mouse models and are critical issues that need to be addressed. As distinct defects exist in each model, we need to be cautious about the experimental design and interpretation of the outcomes obtained using humanized mice. Considering this point, we mainly characterize the current conventional humanized mouse reconstituted only with HSCs and describe past achievements in this area, as well as the potential contributions of the humanized mouse models for the study of HIV pathogenesis and therapy. We also discuss the use of various technologies to solve the current problems. Humanized mice will contribute not only to the pre-clinical evaluation of anti-HIV regimens, but also to a deeper understanding of basic aspects of HIV biology.
AbstractList A variety of humanized mice, which are reconstituted only with human hematopoietic stem cells (HSC) or with fetal thymus and HSCs, have been developed and widely utilized as in vivo animal models of HIV-1 infection. The models represent some aspects of HIV-mediated pathogenesis in humans and are useful for the evaluation of therapeutic regimens. However, there are several limitations in these models, including their incomplete immune responses and poor distribution of human cells to the secondary lymphoid tissues. These limitations are common in many humanized mouse models and are critical issues that need to be addressed. As distinct defects exist in each model, we need to be cautious about the experimental design and interpretation of the outcomes obtained using humanized mice. Considering this point, we mainly characterize the current conventional humanized mouse reconstituted only with HSCs and describe past achievements in this area, as well as the potential contributions of the humanized mouse models for the study of HIV pathogenesis and therapy. We also discuss the use of various technologies to solve the current problems. Humanized mice will contribute not only to the pre-clinical evaluation of anti-HIV regimens, but also to a deeper understanding of basic aspects of HIV biology.
A variety of humanized mice, which are reconstituted only with human hematopoietic stem cells (HSC) or with fetal thymus and HSCs, have been developed and widely utilized as in vivo animal models of HIV-1 infection. The models represent some aspects of HIV-mediated pathogenesis in humans and are useful for the evaluation of therapeutic regimens. However, there are several limitations in these models, including their incomplete immune responses and poor distribution of human cells to the secondary lymphoid tissues. These limitations are common in many humanized mouse models and are critical issues that need to be addressed. As distinct defects exist in each model, we need to be cautious about the experimental design and interpretation of the outcomes obtained using humanized mice. Considering this point, we mainly characterize the current conventional humanized mouse reconstituted only with HSCs and describe past achievements in this area, as well as the potential contributions of the humanized mouse models for the study of HIV pathogenesis and therapy. We also discuss the use of various technologies to solve the current problems. Humanized mice will contribute not only to the pre-clinical evaluation of anti-HIV regimens, but also to a deeper understanding of basic aspects of HIV biology.A variety of humanized mice, which are reconstituted only with human hematopoietic stem cells (HSC) or with fetal thymus and HSCs, have been developed and widely utilized as in vivo animal models of HIV-1 infection. The models represent some aspects of HIV-mediated pathogenesis in humans and are useful for the evaluation of therapeutic regimens. However, there are several limitations in these models, including their incomplete immune responses and poor distribution of human cells to the secondary lymphoid tissues. These limitations are common in many humanized mouse models and are critical issues that need to be addressed. As distinct defects exist in each model, we need to be cautious about the experimental design and interpretation of the outcomes obtained using humanized mice. Considering this point, we mainly characterize the current conventional humanized mouse reconstituted only with HSCs and describe past achievements in this area, as well as the potential contributions of the humanized mouse models for the study of HIV pathogenesis and therapy. We also discuss the use of various technologies to solve the current problems. Humanized mice will contribute not only to the pre-clinical evaluation of anti-HIV regimens, but also to a deeper understanding of basic aspects of HIV biology.
Author Iwabuchi, Ryutaro
Tsunetsugu-Yokota, Yasuko
Terahara, Kazutaka
AuthorAffiliation 2 Department of Life Science and Medical Bioscience, Waseda University, Tokyo 162-8480, Japan
3 Department of Medical Technology, School of Human Sciences, Tokyo University of Technology, Tokyo 144-8535, Japan
1 Research Center for Drug and Vaccine Development, National Institute of Infectious Diseases, Tokyo 162-8640, Japan; tera@nih.go.jp (K.T.); buchitaro@toki.waseda.jp (R.I.)
AuthorAffiliation_xml – name: 3 Department of Medical Technology, School of Human Sciences, Tokyo University of Technology, Tokyo 144-8535, Japan
– name: 1 Research Center for Drug and Vaccine Development, National Institute of Infectious Diseases, Tokyo 162-8640, Japan; tera@nih.go.jp (K.T.); buchitaro@toki.waseda.jp (R.I.)
– name: 2 Department of Life Science and Medical Bioscience, Waseda University, Tokyo 162-8480, Japan
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  givenname: Kazutaka
  surname: Terahara
  fullname: Terahara, Kazutaka
– sequence: 2
  givenname: Ryutaro
  surname: Iwabuchi
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  givenname: Yasuko
  surname: Tsunetsugu-Yokota
  fullname: Tsunetsugu-Yokota, Yasuko
BackLink https://www.ncbi.nlm.nih.gov/pubmed/33924786$$D View this record in MEDLINE/PubMed
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pathogenesis
HIV infection
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immunological features
humanized mice
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SubjectTerms Animal models
Animals
Antigens
antiretroviral agents
Bone Marrow
Cytokines
Disease Models, Animal
experimental design
Fetuses
Genotype & phenotype
Hematopoietic Stem Cell Transplantation
Hematopoietic Stem Cells
HIV
HIV infection
HIV infections
HIV Infections - drug therapy
HIV Infections - physiopathology
HIV-1 - drug effects
HIV-1 - pathogenicity
HIV-1 - physiology
Human immunodeficiency virus
humanized mice
Humans
Immune response
immunological features
Immunology
Infections
Liver
Lymphatic system
Lymphocytes
Lymphoid tissue
Mice
Mice, Inbred Strains
Mice, Transgenic
non-BLT
Pathogenesis
Review
Rodents
Spleen
Stem cell transplantation
Stem cells
therapeutics
therapy
Thymus Gland
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Title Perspectives on Non-BLT Humanized Mouse Models for Studying HIV Pathogenesis and Therapy
URI https://www.ncbi.nlm.nih.gov/pubmed/33924786
https://www.proquest.com/docview/2532402385
https://www.proquest.com/docview/2520869841
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https://pubmed.ncbi.nlm.nih.gov/PMC8145733
https://doaj.org/article/920733756d1c47aea7537a1d31318ef7
Volume 13
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