Age-dependent appearance of SARS-CoV-2 entry cells in mouse chemosensory systems reflects COVID-19 anosmia and ageusia symptoms.

COVID-19 pandemic has given rise to a collective scientific effort to study its viral causing agent SARS-CoV-2. Research is focusing in particular on its infection mechanisms and on the associated-disease symptoms. Interestingly, this environmental pathogen directly affects the human chemosensory systems leading to anosmia and ageusia. Evidence for the presence of the cellular entry sites of the virus, the ACE2 and the TMPRSS2 proteins, has been reported in non-chemosensory cells in the nose and mouth of the rodents, missing a direct correlation between the symptoms reported in patients and the observed direct viral infection in human sensory cells. Here, mapping the gene and protein expression of ACE2 and TMPRSS2 in the mouse olfactory and gustatory cells, we precisely identified the virus target cells to be of basal and sensory origin and we revealed their age-dependent appearance. Our results not only clarify human viral-induced sensory symptoms but also propose new investigative perspectives based on ACE2-humanized mouse models.

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Age-dependent appearance of SARS-CoV-2 entry sites in mouse chemosensory systems reflects COVID-19 anosmia-ageusia symptoms

Communications Biology ◽

10.1038/s42003-021-02410-9 ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Julien Brechbühl ◽

Ana Catarina Lopes ◽

Dean Wood ◽

Sofiane Bouteiller ◽

Aurélie de Vallière ◽

...

Keyword(s):

Animal Models ◽

Viral Entry ◽

Alternative Interpretation ◽

Sensory Cells ◽

Target Cells ◽

Disease Symptoms ◽

Gene And Protein Expression ◽

Age Dependent ◽

Infection Mechanisms ◽

Chemosensory Systems

AbstractCOVID-19 pandemic has given rise to a collective scientific effort to study its viral causing agent SARS-CoV-2. Research is focusing in particular on its infection mechanisms and on the associated-disease symptoms. Interestingly, this environmental pathogen directly affects the human chemosensory systems leading to anosmia and ageusia. Evidence for the presence of the cellular entry sites of the virus, the ACE2/TMPRSS2 proteins, has been reported in non-chemosensory cells in the rodent’s nose and mouth, missing a direct correlation between the symptoms reported in patients and the observed direct viral infection in human sensory cells. Here, mapping the gene and protein expression of ACE2/TMPRSS2 in the mouse olfactory and gustatory cells, we precisely identify the virus target cells to be of basal and sensory origin and reveal the age-dependent appearance of viral entry-sites. Our results propose an alternative interpretation of the human viral-induced sensory symptoms and give investigative perspectives on animal models.

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

Viruses ◽

10.3390/v13050776 ◽

2021 ◽

Vol 13 (5) ◽

pp. 776

Author(s):

Kazutaka Terahara ◽

Ryutaro Iwabuchi ◽

Yasuko Tsunetsugu-Yokota

Keyword(s):

Mouse Models ◽

Humanized Mice ◽

Lymphoid Tissues ◽

Humanized Mouse ◽

Hiv Pathogenesis ◽

Hematopoietic Stem ◽

Critical Issues ◽

In Vivo Animal Models ◽

Humanized Mouse Models

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.

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Humanized Mouse Models to Study Cell-Mediated Immune Responses to Liver-Stage Malaria Vaccines

Trends in Parasitology ◽

10.1016/j.pt.2015.06.008 ◽

2015 ◽

Vol 31 (11) ◽

pp. 583-594 ◽

Cited By ~ 15

Author(s):

Michael F. Good ◽

Michael T. Hawkes ◽

Stephanie K. Yanow

Keyword(s):

Immune Responses ◽

Mouse Models ◽

Humanized Mouse ◽

Liver Stage ◽

Malaria Vaccines ◽

Humanized Mouse Models

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The Future is NOW for Humanized Mouse Models

Humanized Mice for HIV Research ◽

10.1007/978-1-4939-1655-9_42 ◽

2014 ◽

pp. 531-534

Author(s):

J. Victor Garcia

Keyword(s):

Mouse Models ◽

Humanized Mouse ◽

The Future ◽

Humanized Mouse Models

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Generation of Novel Human Red Blood Cell-Bearing Humanized Mouse Models Based on C3-Deficient NOG Mice

Frontiers in Immunology ◽

10.3389/fimmu.2021.671648 ◽

2021 ◽

Vol 12 ◽

Author(s):

Takuya Yamaguchi ◽

Ikumi Katano ◽

Iyo Otsuka ◽

Ryoji Ito ◽

Misa Mochizuki ◽

...

Keyword(s):

Mouse Models ◽

Complement C3 ◽

Humanized Mouse ◽

Hematopoietic Stem ◽

Gm Csf ◽

Human Red Blood Cells ◽

Mouse Macrophages ◽

C3 Gene ◽

Humanized Mouse Models

Despite recent advances in immunodeficient mouse models bearing human red blood cells (hRBCs), the elimination of circulating hRBCs by residual innate immune systems remains a significant challenge. In this study, we evaluated the role of mouse complement C3 in the elimination of circulating hRBCs by developing a novel NOG substrain harboring a truncated version of the murine C3 gene (NOG-C3ΔMG2-3). Genetic C3 deletion prolonged the survival of transfused hRBCs in the circulation. Chemical depletion and functional impairment of mouse macrophages, using clodronate liposomes (Clo-lip) or gadolinium chloride (GdCl3), respectively, further extended the survival of hRBCs in NOG-C3ΔMG2-3 mice. Low GdCl3 toxicity allowed the establishment of hRBC-bearing mice, in which hRBCs survived for more than 4 weeks with transfusion once a week. In addition, erythropoiesis of human hematopoietic stem cells (hHSCs) was possible in NOG-C3ΔMG2-3/human GM-CSF-IL-3 transgenic mice with Clo-lip treatment. These findings indicate that mouse models harboring hRBCs can be achieved using NOG-C3ΔMG2-3 mice, which could facilitate studies of human diseases associated with RBCs.

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