Nef harbors a major determinant of pathogenicity for an AIDS-like disease induced by HIV-1 in transgenic mice

被引：407
作者：
Hanna, Z
Kay, DG
Rebai, N
Guimond, A
Jothy, S
Jolicoeur, P [1 ]
机构：
[1] Clin Res Inst Montreal, Mol Biol Lab, Montreal, PQ H2W 1R7, Canada
[2] Univ Montreal, Dept Med, Montreal, PQ H3C 3J7, Canada
[3] Univ Montreal, Dept Microbiol & Immunol, Montreal, PQ H3C 3J7, Canada
[4] McGill Univ, Dept Pathol, Montreal, PQ H3G 1A4, Canada
[5] McGill Univ, Dept Expt Med, Montreal, PQ H3G 1A4, Canada
[6] Univ Toronto, Dept Lab Med & Pathol, Toronto, ON M5G 1L5, Canada
来源：
CELL | 1998年 / 95卷 / 02期
关键词：
D O I：
10.1016/S0092-8674(00)81748-1
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Transgenic (Tg) mice expressing the complete coding sequences of HIV-1 in CD4(+) T cells and in cells of the macrophage/dendritic lineages develop severe AIDS-like pathologies: failure to thrive/weight loss, diarrhea, wasting, premature death, thymus atrophy, loss of CD4(+) T cells, interstitial pneumonitis, and tubulo-interstitial nephritis. The generation of Tg mice expressing selected HIV-1 gene(s) revealed that nef harbors a major disease determinant. The latency and progression (fast/slow) of the disease were strongly correlated with the levels of Tg expression. Nef-expressing Tg thymocytes were activated and alpha-CD3 hyperresponsive with respect to tyrosine phosphorylation of several substrates, including LAT and MAPK. The similarity of this mouse model to human AIDS, particularly pediatric AIDS, suggests that Nef may play a critical role in human AIDS, independently of its role in virus replication.
引用
收藏
页码：163 / 175
页数：13
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