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Article

Comparing Current and Next-Generation Humanized Mouse Models for Advancing HIV and HIV/Mtb Co-Infection Studies

1
McMaster Immunology Research Centre, Michael G. DeGroote Institute for Infectious Disease Research, Department of Medicine, McMaster University, Hamilton, ON L8S 4K1, Canada
2
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON L8N 3Z5, Canada
3
Axe des Maladies Infectieuses et Immunitaires, Centre de Recherche du CHU de Québec-Université Laval, Pavillon CHUL, Québec City, QC G1V 4G2, Canada
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Caijun Sun
Viruses 2022, 14(9), 1927; https://doi.org/10.3390/v14091927
Received: 8 August 2022 / Accepted: 26 August 2022 / Published: 30 August 2022
(This article belongs to the Special Issue In Vivo Mouse Models of Human Viral Infections)
In people living with HIV, Mycobacterium tuberculosis (Mtb) is the major cause of death. Due to the increased morbidity/mortality in co-infection, further research is urgently required. A limiting factor to research in HIV and HIV/Mtb co-infection is the lack of accessible in vivo models. Next-generation humanized mice expressing HLA transgenes report improved human immune reconstitution and functionality, which may better recapitulate human disease. This study compares well-established huNRG mice and next-generation HLA I/II-transgenic (huDRAG-A2) mice for immune reconstitution, disease course, and pathology in HIV and TB. HuDRAG-A2 mice have improved engraftment of key immune cell types involved in HIV and TB disease. Upon intravaginal HIV-1 infection, both models developed significant HIV target cell depletion in the blood and tissues. Upon intranasal Mtb infection, both models sustained high bacterial load within the lungs and tissue dissemination. Some huDRAG-A2 granulomas appeared more classically organized, characterized by focal central necrosis, multinucleated giant cells, and foamy macrophages surrounded by a halo of CD4+ T cells. HIV/Mtb co-infection in huNRG mice trended towards worsened TB pathology and showed potential for modeling co-infection. Both huNRG and huDRAG-A2 mice are viable options for investigating HIV and TB, but the huDRAG-A2 model may offer advantages. View Full-Text
Keywords: HIV; TB; humanized mice; mouse models of infectious disease HIV; TB; humanized mice; mouse models of infectious disease
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MDPI and ACS Style

Lepard, M.; Yang, J.X.; Afkhami, S.; Nazli, A.; Zganiacz, A.; Tang, S.; Choi, M.W.Y.; Vahedi, F.; Deshiere, A.; Tremblay, M.J.; Xing, Z.; Kaushic, C.; Gillgrass, A. Comparing Current and Next-Generation Humanized Mouse Models for Advancing HIV and HIV/Mtb Co-Infection Studies. Viruses 2022, 14, 1927. https://doi.org/10.3390/v14091927

AMA Style

Lepard M, Yang JX, Afkhami S, Nazli A, Zganiacz A, Tang S, Choi MWY, Vahedi F, Deshiere A, Tremblay MJ, Xing Z, Kaushic C, Gillgrass A. Comparing Current and Next-Generation Humanized Mouse Models for Advancing HIV and HIV/Mtb Co-Infection Studies. Viruses. 2022; 14(9):1927. https://doi.org/10.3390/v14091927

Chicago/Turabian Style

Lepard, Madeleine, Jack X. Yang, Sam Afkhami, Aisha Nazli, Anna Zganiacz, Shangguo Tang, Margaret Wa Yan Choi, Fatemah Vahedi, Alexandre Deshiere, Michel J. Tremblay, Zhou Xing, Charu Kaushic, and Amy Gillgrass. 2022. "Comparing Current and Next-Generation Humanized Mouse Models for Advancing HIV and HIV/Mtb Co-Infection Studies" Viruses 14, no. 9: 1927. https://doi.org/10.3390/v14091927

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