Nef modulation of HIV type 1 gene expression and cytopathicity in tissues of HIV transgenic mice.
Nef modulation of HIV type 1 gene expression and cytopathicity in tissues of HIV transgenic mice.
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Nef 对 HIV 转基因小鼠组织中 HIV 1 型基因表达和细胞病变的调节。
DOI：
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发表时间：
2000
影响因子：
1.5
通讯作者：
P. Dickie
中科院分区：
文献类型：
--
作者：
P. Dickie
携带gag/pol区缺失的HIV-1前病毒DNA的转基因小鼠（HIVd 1443小鼠）在包括巨噬细胞在内的各种细胞类型中模拟了一种慢性、非生产性形式的病毒基因表达。它们表现出的疾病表型包括HIV相关肾病（HIVAN）、先天性白内障、乳头状瘤病和生长障碍。HIV-1 Nef在病毒基因调控和疾病发展中的作用在携带同基因HIV转基因的小鼠中进行了探索，其中nef通过移码突变而突变。与Nef+小鼠一样，HIVd 1443 [Nef-]小鼠在皮肤、肌肉、肾脏和腹腔巨噬细胞中表达HIV基因产物。虽然这些小鼠没有发生白内障、乳头状瘤性皮肤病变或显示任何明显的生长缺陷，但它们确实发生了HIVAN。通过与携带HIV LTR连锁nef转基因的小鼠交配，将Nef表达引入HIVd 1443 [Nef-]小鼠。Nef补充的HIVd 1443 [Nef-]小鼠肌肉和肾脏中的病毒基因产物水平降低。相比之下，这些小鼠皮肤中的HIV基因表达仍然很高，并且出现的乳头状瘤病变比野生型HIVd 1443小鼠更严重。尽管如此，Nef对LPS诱导的可见正常皮肤中的病毒基因表达有负面影响。在腹膜巨噬细胞的比较中，病毒RNA表达在Nef+小鼠的常驻巨噬细胞中显著降低。HIV炎性巨噬细胞表达病毒基因并显示改变的FACS谱。特别是，Nef+群体的标志是F4/80 med/Mac-1-细胞比例增加以及Mac-1细胞减少和F4/80染色减少。这种HIV前病毒转基因模型已经证明了HIV-1 Nef通过改变体内细胞成熟和病毒基因表达而导致HIV细胞病变的能力。
Transgenic mice bearing HIV-1 proviral DNA deleted in the gag/pol region (HIVd1443 mice) model a chronic, nonproductive form of viral gene expression in various cell types including macrophages. They display a disease phenotype that includes HIV-associated nephropathy (HIVAN), congenital cataracts, papillomatosis, and growth failure. The role of HIV-1 Nef in viral gene regulation and the development of disease was explored in mice bearing an isogenic HIV transgene in which nef was mutated by frameshift mutation. Like its Nef+ counterpart, HIVd1443[Nef-] mice expressed HIV gene products in the skin, muscle, kidney, and peritoneal macrophages. While these mice did not develop cataracts, papillomatous skin lesions, or display any apparent growth defect, they did develop HIVAN. Nef expression was introduced to HIVd1443[Nef-] mice through breeding to mice bearing an HIV LTR-linked nef transgene. Nef-complemented HIVd1443[Nef-] mice had reduced levels of viral gene products in the muscle and kidney. In contrast, HIV gene expression in the skin of these mice remained high and papillomatous lesions emerged that were more severe than those on wild-type HIVd1443 mice. Still, Nef had a negative effect on LPS-induced viral gene expression in visibly normal skin. In comparisons of peritoneal macrophages, viral RNA expression was significantly reduced in resident macrophages of Nef+ mice. HIV inflammatory macrophages expressed viral genes and displayed an altered FACS profile. In particular, Nef+ populations were marked by an increased proportion of F4/80med/Mac-1-cells as well as fewer Mac-1 cells and reduced F4/80 staining. This HIV proviral transgenic model has demonstrated the capacity of HIV-1 Nef to contribute to HIV cytopathicity by altering cellular maturation and viral gene expression in vivo.
人类免疫缺陷病毒 1 型 Nef 与 T 淋巴细胞中的细胞丝氨酸激酶相关。
DOI：
10.1073/pnas.91.4.1539
发表时间：
1994
影响因子：
11.1
作者：
Sawai,ET;Baur,A;Struble,H;Peterlin,BM;Levy,JA;Cheng-Mayer,C
通讯作者：
Cheng-Mayer,C
影响因子：
56.9
作者：
Finzi, D;Hermankova, M;Siliciano, RF
通讯作者：
Siliciano, RF
涉及淋巴耗竭的 HIV 基因的转基因解剖。
DOI：
10.1172/jci119518
发表时间：
1997
期刊：
The Journal of clinical investigation.
影响因子：
--
作者：
Tinkle,BT;Ueda,H;Ngo,L;Luciw,PA;Shaw,K;Rosen,CA;Jay,G
通讯作者：
Jay,G