Details

Autor(en) / Beteiligte

• Keppler, Oliver T
• Welte, Frank J
• Ngo, Tuan A
• Chin, Peggy S
• Patton, Kathryn S
• Tsou, Chia-Lin
• Abbey, Nancy W
• Sharkey, Mark E
• Grant, Robert M
• You, Yun
• Scarborough, John D
• Ellmeier, Wilfried
• Littman, Dan R
• Stevenson, Mario
• Charo, Israel F
• Herndier, Brian G
• Speck, Roberto F
• Goldsmith, Mark A

Titel

Progress toward a human CD4/CCR5 transgenic rat model for de novo infection by human immunodeficiency virus type 1

Ist Teil von

• The Journal of experimental medicine, 2002-03, Vol.195 (6), p.719-736

Ort / Verlag

United States: The Rockefeller University Press

Erscheinungsjahr

2002

Quelle

Elektronische Zeitschriftenbibliothek

Beschreibungen/Notizen

• 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.