Lymphoid organs as a major reservoir for human T-cell leukemia virus type 1 in experimentally infected squirrel monkeys (Saimiri sciureus):: Provirus expression, persistence, and humoral and cellular immune responses
Lymphoid organs as a major reservoir for human T-cell leukemia virus type 1 in experimentally infected squirrel monkeys (Saimiri sciureus):: Provirus expression, persistence, and humoral and cellular immune responses
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DOI：
10.1128/jvi.74.10.4860-4867.2000
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发表时间：
2000-05-01
影响因子：
5.4
通讯作者：
de Thé, G
中科院分区：
文献类型：
--
作者：
Kazanji, M;Ureta-Vidal, A;de Thé, G
本研究的目的是调查人类 T 细胞白血病病毒 1 型 (HTLV-1) 在连续处死的松鼠猴 (Saimiri sciureus) 的各个器官中的分布，以定位病毒储存库并评估感染期间病毒表达与体液或细胞免疫反应之间的关系。接种HTLV-1后6、12、35天和3、6、26个月处死感染HTLV-1的6只松鼠猴，每只动物采集20个器官和组织，用gag和tar引物进行PCR和逆转录PCR（RT-PCR）。通过PCR在接种后6天处死的猴子的外周血单核细胞(PBMC)以及接种后12和35天以及3、6和26个月处死的猴子的PBMC、脾脏和淋巴结中检测到前病毒DNA。此外，通过RT-PCR在接种后8至12天的两只猴子的PBMC中以及在第12天处死的猴子的脾脏和淋巴结中检测到tar/rex mRNA，在该动物中，通过原位杂交在脾脏冰冻切片中、生发中心周围和靠近毛细血管处检测到分散的HTLV-1tax/rex mRNA阳性淋巴细胞。在接种后的不同时间评估抗HTLV-1 Tell介导的免疫。感染后 2 个月检测到抗 p40(Tax) 和抗 Env 溶细胞 T 细胞反应，并且此后仍可检测到。当使用 Tax 肽时，这种反应似乎针对各种 Tax 表位。我们的结果表明，松鼠猴代表了一种有前途的动物模型，可用于研究 HTLV-1 感染的早期事件和评估针对 HTLV-1 的候选疫苗。
The aim of this study was to investigate the distribution of human T-cell leukemia virus type 1 (HTLV-1) in various organs of serially sacrificed squirrel monkeys (Saimiri sciureus) in order to localize the reservoir of the virus and to evaluate the relationship between viral expression and the humoral or cellular immune response during infection. Six squirrel monkeys infected with HTLV-1 were sacrificed 6, 12, and 35 days and 3, 6, and 26 months after inoculation and 20 organs and tissues were collected from each animal, PCR and reverse transcription-PCR (RT-PCR) were performed with gag and tar primers. Proviral DNA was detected by PCR in peripheral blood mononuclear cells (PBMCs) of monkeys sacrificed 6 days after inoculation and in PBMCs, spleens, and lymph nodes of monkeys sacrificed 12 and 35 days and 3, 6, and 26 months after inoculation. Furthermore, tar/rex mRNA was detected by RT-PCR in the PBMCs of two monkeys 8 to 12 days after inoculation and in the spleens and lymph nodes of the monkey sacrificed on day 12, in this animal, scattered HTLV-1 tax/rex mRNA-positive lymphocytes were detected by in situ hybridization in frozen sections of the spleen, around the germinal centers and close to the arterial capillaries. Anti-HTLV-1 tell-mediated immunity was evaluated at various times after inoculation. Anti-p40(Tax) and anti-Env cytolytic T-cell responses were detected 2 months after infection and remained detectable thereafter. When Tax peptides were used, this response appeared to be directed against various Tax epitopes, Our results indicate that squirrel monkeys represent a promising animal model for studying the early events of HTLV-1 infection and for evaluating candidate vaccines against HTLV-1.