An Efficient Humanized Mouse Model for Oral Anti-Retroviral Administration
HIV anti-retrovirals (ARVs) have vastly improved the life expectancy of people living with HIV (PLWH). However, toxic effects attributed to long-term ARV use also contribute to HIV-related co-morbidities such as heart disease, bone loss and HIV-associated neurocognitive disorders (HAND). Unfortunate...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-03-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/12/7/1034 |
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| author | Amber K. Virdi Sang Ho Melanie S. Seaton Arnold Z. Olali Srinivas D. Narasipura Hannah J. Barbian Leannie J. Olivares Hemil Gonzalez Lee C. Winchester Anthony T. Podany Ryan D. Ross Lena Al-Harthi Jennillee Wallace |
| author_facet | Amber K. Virdi Sang Ho Melanie S. Seaton Arnold Z. Olali Srinivas D. Narasipura Hannah J. Barbian Leannie J. Olivares Hemil Gonzalez Lee C. Winchester Anthony T. Podany Ryan D. Ross Lena Al-Harthi Jennillee Wallace |
| author_sort | Amber K. Virdi |
| collection | DOAJ |
| description | HIV anti-retrovirals (ARVs) have vastly improved the life expectancy of people living with HIV (PLWH). However, toxic effects attributed to long-term ARV use also contribute to HIV-related co-morbidities such as heart disease, bone loss and HIV-associated neurocognitive disorders (HAND). Unfortunately, mouse models used to study the effects of ARVs on viral suppression, toxicity and HIV latency/tissue reservoirs have not been widely established. Here, we demonstrate an effective mouse model utilizing immune-compromised mice, reconstituted with infected human peripheral blood mononuclear cell (PBMCs). ARVs areincorporated into mouse chow and administered daily with combination ARV regimens includingAtripla (efavirenz, tenofovir disoproxil fumarate, and emtricitabine) and Triumeq (abacavir, dolutegravir and lamivudine). This model measures HIV-infected human cell trafficking, and ARV penetration throughout most relevant HIV organs and plasma, with a large amount of trafficking to the secondary lymphoid organs. Furthermore, the HIV viral load within each organ and the plasma was reduced in ARV treated vs. untreated control. Overall, we have demonstrated a mouse model that is relatively easy and affordable to establish and utilize to study ARVs’ effect on various tissues, including the co-morbid conditions associated with PLWH, such as HAND, and other toxic effects. |
| first_indexed | 2024-03-11T05:41:08Z |
| format | Article |
| id | doaj.art-a3c846cc78b743889acf18674eee8261 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T05:41:08Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-a3c846cc78b743889acf18674eee82612023-11-17T16:28:22ZengMDPI AGCells2073-44092023-03-01127103410.3390/cells12071034An Efficient Humanized Mouse Model for Oral Anti-Retroviral AdministrationAmber K. Virdi0Sang Ho1Melanie S. Seaton2Arnold Z. Olali3Srinivas D. Narasipura4Hannah J. Barbian5Leannie J. Olivares6Hemil Gonzalez7Lee C. Winchester8Anthony T. Podany9Ryan D. Ross10Lena Al-Harthi11Jennillee Wallace12Department of Microbial Pathogens and Immunity, Rush University Medical Center, Chicago, IL 60612, USADepartment of Microbial Pathogens and Immunity, Rush University Medical Center, Chicago, IL 60612, USADepartment of Microbial Pathogens and Immunity, Rush University Medical Center, Chicago, IL 60612, USACenter for Mitochondrial and Epigenomic Medicine, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USADepartment of Microbial Pathogens and Immunity, Rush University Medical Center, Chicago, IL 60612, USADepartment of Internal Medicine, Division of Infectious Diseases, Rush Medical College, Chicago, IL 60612, USADepartment of Microbial Pathogens and Immunity, Rush University Medical Center, Chicago, IL 60612, USADepartment of Microbial Pathogens and Immunity, Rush University Medical Center, Chicago, IL 60612, USAUNMC Center for Drug Discovery, University of Nebraska Medical Center, Omaha, NE 68182, USAUNMC Center for Drug Discovery, University of Nebraska Medical Center, Omaha, NE 68182, USADepartment of Anatomy & Cell Biology, Rush University Medical Center, Chicago, IL 60612, USADepartment of Microbial Pathogens and Immunity, Rush University Medical Center, Chicago, IL 60612, USADepartment of Microbial Pathogens and Immunity, Rush University Medical Center, Chicago, IL 60612, USAHIV anti-retrovirals (ARVs) have vastly improved the life expectancy of people living with HIV (PLWH). However, toxic effects attributed to long-term ARV use also contribute to HIV-related co-morbidities such as heart disease, bone loss and HIV-associated neurocognitive disorders (HAND). Unfortunately, mouse models used to study the effects of ARVs on viral suppression, toxicity and HIV latency/tissue reservoirs have not been widely established. Here, we demonstrate an effective mouse model utilizing immune-compromised mice, reconstituted with infected human peripheral blood mononuclear cell (PBMCs). ARVs areincorporated into mouse chow and administered daily with combination ARV regimens includingAtripla (efavirenz, tenofovir disoproxil fumarate, and emtricitabine) and Triumeq (abacavir, dolutegravir and lamivudine). This model measures HIV-infected human cell trafficking, and ARV penetration throughout most relevant HIV organs and plasma, with a large amount of trafficking to the secondary lymphoid organs. Furthermore, the HIV viral load within each organ and the plasma was reduced in ARV treated vs. untreated control. Overall, we have demonstrated a mouse model that is relatively easy and affordable to establish and utilize to study ARVs’ effect on various tissues, including the co-morbid conditions associated with PLWH, such as HAND, and other toxic effects.https://www.mdpi.com/2073-4409/12/7/1034HIVanti-retroviralmouse modellatencyintegrationhuman cell trafficking |
| spellingShingle | Amber K. Virdi Sang Ho Melanie S. Seaton Arnold Z. Olali Srinivas D. Narasipura Hannah J. Barbian Leannie J. Olivares Hemil Gonzalez Lee C. Winchester Anthony T. Podany Ryan D. Ross Lena Al-Harthi Jennillee Wallace An Efficient Humanized Mouse Model for Oral Anti-Retroviral Administration Cells HIV anti-retroviral mouse model latency integration human cell trafficking |
| title | An Efficient Humanized Mouse Model for Oral Anti-Retroviral Administration |
| title_full | An Efficient Humanized Mouse Model for Oral Anti-Retroviral Administration |
| title_fullStr | An Efficient Humanized Mouse Model for Oral Anti-Retroviral Administration |
| title_full_unstemmed | An Efficient Humanized Mouse Model for Oral Anti-Retroviral Administration |
| title_short | An Efficient Humanized Mouse Model for Oral Anti-Retroviral Administration |
| title_sort | efficient humanized mouse model for oral anti retroviral administration |
| topic | HIV anti-retroviral mouse model latency integration human cell trafficking |
| url | https://www.mdpi.com/2073-4409/12/7/1034 |
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