Progress toward a human CD4/CCR5 transgenic rat model for de novo infection by human immunodeficiency virus type 1
| Autor: | Tuan A. Ngo, Chia-Lin Tsou, Brian G. Herndier, John D. Scarborough, Yun You, Frank J. Welte, Mark A. Goldsmith, Mark Sharkey, Israel F. Charo, Dan R. Littman, Robert M. Grant, Roberto F. Speck, Wilfried Ellmeier, Kathryn S. Patton, Mario Stevenson, Nancy W. Abbey, Peggy S. Chin, Oliver T. Keppler |
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| Rok vydání: | 2002 |
| Předmět: |
Receptor complex
Receptors CCR5 Chemokine receptor CCR5 Transgene Immunology Viremia HIV Infections Virus Replication Animals Genetically Modified 03 medical and health sciences 0302 clinical medicine medicine Immunology and Allergy Animals Humans transgenic rats 030304 developmental biology 0303 health sciences biology Microglia Macrophages Provirus medicine.disease Virology CD4 3. Good health Rats Disease Models Animal medicine.anatomical_structure Viral replication CD4 Antigens biology.protein HIV-1 Original Article CCR5 030217 neurology & neurosurgery Ex vivo |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 0022-1007 |
| Popis: | The development of a permissive small animal model for the study of human immunodeficiency virus type (HIV)-1 pathogenesis and the testing of antiviral strategies has been hampered by the inability of HIV-1 to infect primary rodent cells productively. In this study, we explored transgenic rats expressing the HIV-1 receptor complex as a susceptible host. Rats transgenic for human CD4 (hCD4) and the human chemokine receptor CCR5 (hCCR5) were generated that express the transgenes in CD4+ T lymphocytes, macrophages, and microglia. In ex vivo cultures, CD4+ T lymphocytes, macrophages, and microglia from hCD4/hCCR5 transgenic rats were highly susceptible to infection by HIV-1 R5 viruses leading to expression of abundant levels of early HIV-1 gene products comparable to those found in human reference cultures. Primary rat macrophages and microglia, but not lymphocytes, from double-transgenic rats could be productively infected by various recombinant and primary R5 strains of HIV-1. Moreover, after systemic challenge with HIV-1, lymphatic organs from hCD4/hCCR5 transgenic rats contained episomal 2–long terminal repeat (LTR) circles, integrated provirus, and early viral gene products, demonstrating susceptibility to HIV-1 in vivo. Transgenic rats also displayed a low-level plasma viremia early in infection. Thus, transgenic rats expressing the appropriate human receptor complex are promising candidates for a small animal model of HIV-1 infection. |
| Databáze: | OpenAIRE |
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