A Humanized Mouse Model to Study Hepatitis C Virus Infection, Immune Response, and Liver Disease

Washburn, Michael L.; Bility, Moses T.; Zhang, Liguo; Kovalev, Grigoriy I.; Buntzman, Adam; Frelinger, J. A.; Barry, Walter T.; Ploß, Alexander; Rice, Charles M.; Su, Lishan

doi:10.1053/j.gastro.2011.01.001

Cited by 274 publications

(311 citation statements)

References 40 publications

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“…It has been demonstrated that a human immune system and hepatocytes can be reconstituted in the same humanized mice (26). Similarly, we have shown previously that engraftment of CD34 + cells from fetal liver into NSG mice leads to reconstitution of human immune cells as well as human hepatocytes in the mouse liver (27).…”

Section: Discussionsupporting

confidence: 72%

Human natural killer cells control Plasmodium falciparum infection by eliminating infected red blood cells

Chen

Amaladoss

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Immunodeficient mouse-human chimeras provide a powerful approach to study host-specific pathogens, such as Plasmodium falciparum that causes human malaria. Supplementation of immunodeficient mice with human RBCs supports infection by human Plasmodium parasites, but these mice lack the human immune system. By combining human RBC supplementation and humanized mice that are optimized for human immune cell reconstitution, we have developed RBC-supplemented, immune cell-optimized humanized (RICH) mice that support multiple cycles of P. falciparum infection. Depletion of human natural killer (NK) cells, but not macrophages, in RICH mice results in a significant increase in parasitemia. Further studies in vitro show that NK cells preferentially interact with infected RBCs (iRBCs), resulting in the activation of NK cells and the elimination of iRBCs in a contact-dependent manner. We show that the adhesion molecule lymphocyte-associated antigen 1 is required for NK cell interaction with and elimination of iRBCs. Development of RICH mice and validation of P. falciparum infection should facilitate the dissection of human immune responses to malaria parasite infection and the evaluation of therapeutics and vaccines. malaria infection | humanized mouse model | LFA-1 | NK killing

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Section: Discussionsupporting

confidence: 72%

Human natural killer cells control Plasmodium falciparum infection by eliminating infected red blood cells

Chen

Amaladoss

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…Akute T cell leukemia (ATL) like T cell expansions [59] Dengue virus Leucocyte infection [66] Hepatitis C virus (HCV) Liver disease [69] John Cunningham (JC) virus Persistent infection [71] Influenza A virus Lung infection [72] 1 For clarity only one key reference has been listed Human fetal thymus and liver organoid…”

Section: Discussionmentioning

confidence: 99%

“…This was performed in BRG mice, in which liver damage was induced, by transfer of hepatocyte precursors and HPCs [68]. These mice were then infected with HCV intravenously [69]. Both HCV induced liver damage and induction of HCV specific immune responses could be observed.…”

Section: Flavivirus Infections (Dengue Virus Hcv)mentioning

confidence: 99%

Viral infections in mice with reconstituted human immune system components

Münz

2014

Immunology Letters

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Pathogenic viruses are often difficult to study due to their exclusive tropism for humans. The development of mice with human immune system components opens the possibility to study those human pathogens with a tropism for the human hematopoietic lineage in vivo. These include HCMV, EBV, KSHV, HIV, HTLV-1, dengue virus and JC virus. Furthermore, some human pathogens, like HSV-2, adenovirus, HCV, HBV and influenza A virus, with an additional tropism for somatic mouse tissues or for additional transplanted human tissues, mainly liver, have been explored in these models. The cellular tropism of these viruses, their associated diseases and primarily cell-mediated immune responses to these viral infections will be discussed in this review. Already some exciting information has been gained from these novel chimeric in vivo models and future avenues to gain more insights into the pathology, but also potential therapies, will be outlined. Although the respective in vivo models of human immune responses can still be significantly improved, they already provide preclinical systems for in vivo studies of important viral pathogens of humans. AbstractPathogenic viruses are often difficult to study due to their exclusive tropism for humans. The development of mice with human immune system components opens the possibility to study those human pathogens with a tropism for the human hematopoietic lineage in vivo. These include HCMV, EBV, KSHV, HIV, HTLV-1, dengue virus and JC virus. Furthermore, some human pathogens, like HSV-2, adenovirus, HCV, HBV and influenza A virus, with an additional tropism for somatic mouse tissues or for additional transplanted human tissues, mainly liver, have been explored in these models. The cellular tropism of these viruses, their associated diseases and primarily cell-mediated immune responses to these viral infections will be discussed in this review. Already some exciting information has been gained from these novel chimeric in vivo models and future avenues to gain more insights into the pathology, but also potential therapies, will be outlined. Although the respective in vivo models of human immune responses can still be significantly improved, they already provide preclinical systems for in vivo studies of important viral pathogens of humans.Christian Münz 3 Mice with reconstituted human immune system components as models of human immune responsesHuman immune responses can be studied in a correlative fashion in only a few tissues, which can be biopsied from patients or healthy individuals, including peripheral blood, some secondary lymphoid tissues, like tonsils, and the tumor microenvironment, assessing tumor infiltrating lymphocytes (TILs). For a more systematic analysis and in order to study the outcome of manipulations during immune responses, immunologists have primarily turned to the mouse as an in vivo animal model of mammalian immune responses. However, with a more and more detailed analysis of the mouse immune system it has become apparent that significant differences in ...

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“…Enfin, le système immunitaire de la souris doit être, lui aussi, humanisé, pour espérer reproduire toute la physiopathologie de la maladie. Ces différents critères semblent désormais réunis dans un modèle qui vient d'être publié dans la revue Gastroenterology [7]. L'animal receveur est une souris transgénique exprimant dans ses hépatocy-tes une caspase 8 dimérisable et donc L'infection de cette souris immunodé-primée par le VHC n'a été que récemment démontrée [6].…”

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Des souris humanisées pour l’étude du virus de l’hépatite C

Gilgenkrantz

2011

Med Sci (Paris)

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A Humanized Mouse Model to Study Hepatitis C Virus Infection, Immune Response, and Liver Disease

Cited by 274 publications

References 40 publications

Human natural killer cells control Plasmodium falciparum infection by eliminating infected red blood cells

Human natural killer cells control Plasmodium falciparum infection by eliminating infected red blood cells

Viral infections in mice with reconstituted human immune system components

Des souris humanisées pour l’étude du virus de l’hépatite C

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