Mice transgenic for human CD4 and CCR5 are susceptible to HIV infection

Jessie Browning, James W. Horner, Massimo Pettoello-Mantovani, Christina Raker, Sergey Yurasov, Ronald A. Depinho, Harris Goldstein

Research output: Contribution to journalArticle

103 Citations (Scopus)

Abstract

HIV entry into human cells is mediated by CD4 acting in concert with one of several members of the chemokine receptor superfamily. The resistance to HIV infection observed in individuals with defective CCR5 alleles indicated that this particular chemokine receptor plays a crucial role in the initiation of in vivo HIV infection. Expression of human CD4 transgene does not render mice susceptible to HIV infection because of structural differences between human and mouse CCR5. To ascertain whether expression of human CD4 and CCR5 is sufficient to make murine T lymphocytes susceptible to HIV infection, the lck promoter was used to direct the T cell-specific expression of human CD4 and CCR5 in transgenic mice. Peripheral blood mononuclear cells and splenocytes isolated from these mice expressed human CD4 and CCR5 and were infectible with selected M-tropic HIV isolates. After in vivo inoculation, HIV-infected cells were detected by DNA PCR in the spleen and lymph nodes of these transgenic mice, but HIV could not be cultured from these cells. This indicated that although transgenic expression of human CD4 and CCR5 permitted entry of HIV into the mouse cells significant HIV infection was prevented by other blocks to HIV replication present in mouse cells. In addition to providing in vivo verification for the important role of CCR5 in T lymphocyte HIV infection, these transgenic mice represent a new in vivo model for understanding HIV pathogenesis by delineating species- specific cellular factors required for productive in vivo HIV infection. These mice should also prove useful for the assessment of potential therapeutic and preventative modalities, particularly vaccines.

Original languageEnglish (US)
Pages (from-to)14637-14641
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume94
Issue number26
DOIs
StatePublished - Dec 23 1997

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Transgenic Mice
HIV Infections
HIV
Chemokine Receptors
T-Lymphocytes
Transgenes
Cultured Cells
Blood Cells
Vaccines
Spleen
Lymph Nodes
Alleles
Polymerase Chain Reaction
DNA

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Mice transgenic for human CD4 and CCR5 are susceptible to HIV infection. / Browning, Jessie; Horner, James W.; Pettoello-Mantovani, Massimo; Raker, Christina; Yurasov, Sergey; Depinho, Ronald A.; Goldstein, Harris.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 94, No. 26, 23.12.1997, p. 14637-14641.

Research output: Contribution to journalArticle

Browning, Jessie ; Horner, James W. ; Pettoello-Mantovani, Massimo ; Raker, Christina ; Yurasov, Sergey ; Depinho, Ronald A. ; Goldstein, Harris. / Mice transgenic for human CD4 and CCR5 are susceptible to HIV infection. In: Proceedings of the National Academy of Sciences of the United States of America. 1997 ; Vol. 94, No. 26. pp. 14637-14641.
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