科学发现"北平顶猴"是较理想艾滋病模型动物


科学发现"北平顶猴"是较理想艾滋病模型动物

 
 
 
 
 

 

科学发现"北平顶猴"是较理想艾滋病模型动物

2009/07/23 10:33    来源:探索网    

北平顶猴又称豚猴,目前野生的数量估计总数不足1000只
北平顶猴又称豚猴,目前野生的数量估计总数不足1000只

  近日,在国家“973”项目、国家自然科学基金和NSFC—云南联合基金等项目的资助下,中国科学院昆明动物研究所动物模型与人类疾病机理重点实验室研究员郑永唐学科组在北平顶猴天然免疫分子TRIM5基因和HIV-1感染的相关性研究中获重要进展,进一步阐明了TRIM5α限制HIV-1感染和复制的作用机制,并表明北平顶猴是较理想的艾滋病模型动物。


  据郑永唐介绍,理想的动物模型对艾滋病的发病机制、抗HIV药物及疫苗等研究具有特别重要的作用,但至今国际上尚未建立理想的动物模型。非人灵长类动物是目前公认较理想的艾滋病模型动物,黑猩猩是与人类亲缘关系最近的灵长类动物。有研究报道,黑猩猩可以感染HIV-1并出现人艾滋病样症状。


  然而,黑猩猩是高度濒危物种,而且体型巨大,不易繁殖和养育,费用昂贵,难以作为艾滋病研究动物模型。新大陆灵长类动物除鹰猴外均可支持HIV-1的复制,但HIV-1进入宿主细胞的水平很低,并且新大陆猴中的所有种类均为珍稀保护动物,资源极其匮乏,中国也没有资源和分布。旧大陆猴的资源相对丰富,但在所研究的旧大陆猴中,平顶猴是国际上有报道唯一可感染HIV-1并伴有艾滋病样症状发生的灵长类动物,但其确切机制有待探索。

 TRIM5α是2004年发现的一个重要的宿主细胞天然免疫分子。在灵长类动物中,TRIM5α蛋白限制了HIV-1、N型鼠白血病病毒、马传染性贫血病病毒等逆转录病毒的复制。郑永唐学科组和宿兵学科组的前期合作研究首先发现,平顶猴TRIM5基因座中插入了亲环蛋白A基因,形成TRIM5-CypA融合模式,该融合基因产物不能限制HIV-1的复制,这可能是平顶猴易感HIV-1的重要分子基础。


  然而,根据现行的灵长类动物分类学,2001年动物分类学家将原猕猴属平顶猴中3个亚种提升为3个不同种——巽他平顶猴(Sunda pig-tailed macaque,M.nemestrina)、北平顶猴(Northern pig-tailed macaque,M.leonine)和明打威猴(Mentawai macaque,M.pagensis),而北平顶猴仅分布于我国云南南部和西藏东南部以及缅甸、泰国和印度北部地区。


  在郑永唐的指导下,该学科组博士研究生况轶群等人研究发现,中国云南境内北平顶猴都存在CypA假基因的cDNA通过逆转座机制插入至TRIM5基因座的3’非翻译区的现象,形成了一个新型融合基因npmTRIMCyp。npmTRIMCyp融合基因转录本中外显子7和8均被剪切掉。外显子7剪接丢失机制源于TRIM5第6内含子内3’剪接位点的G/T突变。

  同时发现,北平顶猴外周血单个核细胞对HIV-1易感,不限制HIV-1在细胞内的复制;npmTRIMCyp融合蛋白可以有效地限制HIV-2的复制,对猴免疫缺陷病毒则只有十分微弱的限制活性;北平顶猴npmTRIMCyp可能识别逆转录病毒衣壳蛋白的区域存在较高的多态性。这些研究结果进一步阐明了天然免疫分子TRIM5α限制HIV-1感染和复制的作用机制,在细胞和分子水平上支持了北平顶猴是较理想的艾滋病模型动物,为建立基于北平顶猴的艾滋病灵长类动物模型提供了科学依据。日前,国际学术期刊《逆转录病毒学》发表了该项研究结果。


  据了解,中国境内北平顶猴分布狭窄,现存数量稀少,估计野外总数不足1000只。为此,郑永唐建议有关部门加强对野生北平顶猴的保护,支持相关机构进行人工饲养繁殖和扩大种群,为我国科技自主创新、疾病防控和人类健康提供强有力的支撑。

Scientific discovery, "Peking top monkey" is a better animal model for AIDS
2009/07/23 10:33 Source: explore network


Top Beiping monkey monkey, also known as dolphin, the current number of wild under-estimate the total number of 1000
Recently, at the national "973" project, National Natural Science Foundation of NSFC-and co-fund the project in Yunnan Province, with financial support from Chinese Academy of Sciences, Kunming Institute of Zoology, animal model and the mechanism of human disease researcher Yong Tang Key Laboratory in Beijing Top-disciplinary group of monkeys innate immune molecules TRIM5 genes and HIV-1 infection has been important progress in the study, and further clarified the TRIM5α restricted HIV-1 infection and replication mechanism, and that Beijing is the top of the monkey AIDS model for better animal.


According to Tang Yong, the ideal animal model for the pathogenesis of AIDS, anti-HIV drugs and vaccine research is a particularly important role, but so far the international community has not yet been established animal model of an ideal. Non-human primates is currently recognized as a better animal model of AIDS, chimpanzee and human relationships is the most recent primates. Studies have reported that chimpanzees can be infected with HIV-1 and human AIDS-like symptoms appear.


However, chimpanzees are highly endangered species, but also a great size, easy breeding and rearing, the cost of expensive, difficult to study as an animal model of AIDS. In addition to the New World primates monkeys outside the Eagle would be able to support HIV-1 replication, but the HIV-1 into the low level of host cells, and the New World monkeys of all types are rare and protected species, extremely scarce resources, China has not and distribution of resources. Old World monkeys of the relative abundance of resources, but research in the Old World monkey, the flat-topped monkey, there is only reported HIV-1 infection and with AIDS-like symptoms occurred in primates, but its exact mechanism to be explored.

In 2004 found that TRIM5α is an important host cell innate immune molecules. In primates, TRIM5α protein restricted HIV-1, N-type murine leukemia virus, equine infectious anemia virus replication retrovirus. ZHENG Yong-Tang-disciplinary group and places the pre-soldiers-disciplinary research team first found that flat-topped monkey TRIM5 locus by inserting a gene cyclophilin A to form a TRIM5-CypA fusion model, the fusion gene product can not restrict HIV-1 replication This may be flat-topped monkey susceptible HIV-1 molecular basis of important.


However, according to the existing primate taxonomy, animal taxonomists in 2001 the original flat-topped monkey Macaca three subspecies in the upgrading of three different types - flat-topped monkey Sunda (Sunda pig-tailed macaque, M.nemestrina), Peking top monkey (Northern pig-tailed macaque, M.leonine) and Ming-wei monkey fight (Mentawai macaque, M.pagensis), and Beijing is only distributed in the top monkey in southern China's Yunnan and southeastern Tibet and Myanmar, the northern region of Thailand and India.


ZHENG Yong-Tang in, under the guidance of the subject group the status of doctoral students and others study found Yiqun, China Yunnan Top Beiping monkey CypA pseudogene exists through the reversal of the cDNA insert to block the mechanism of TRIM5 locus 3 'untranslated region of the phenomenon, formed a new fusion gene npmTRIMCyp. fusion gene transcripts npmTRIMCyp foreign exons 7 and 8 have been cut off. Exon 7 splicing mechanism stems from the loss of TRIM5 intron 6 within the first 3 'splice site of the G / T mutation.

At the same time, Beijing top monkey peripheral blood mononuclear cells susceptible to HIV-1 does not restrict HIV-1 replication in cells; npmTRIMCyp fusion protein can effectively limit the replication of HIV-2, simian immunodeficiency virus for only a very weak restrictions on activity; Beiping top monkey may npmTRIMCyp retroviral capsid protein to identify regions of high polymorphism. The results of these studies further elucidate the innate immune molecules TRIM5α restricted HIV-1 infection and replication mechanism, in the cellular and molecular level in support of a top Peking monkey AIDS is an ideal animal model for the establishment of a monkey on top of AIDS Beiping Ling Cheung type of animal model provides a scientific basis. A few days ago, the international academic journal, "retroviral virology," published the results of the study.


It is understood that the top monkey in China Peking narrow distribution, the number of existing scarce, it is estimated that less than 1000 wild. To this end, Yong Tang proposed to enhance the top of wild monkeys Beiping protection, support of relevant agencies and the expansion of artificial breeding populations of independent innovation of China's science and technology, disease prevention and control and human health provide a strong support.
 
 
 
 
 
 

[ 作者:佚名    转贴自:本站原创    点击数:196    更新时间:2009-7-23    文章录入:nnb ]

 

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