WNPRC IMMUNOLOGY & VIROLOGY UNIT

WNPRC 免疫学

• 批准号: 8173096
• 负责人: David I Watkins
• 金额: $ 10.33万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8173096
• 关键词: Acquired Immunodeficiency Syndrome; Affect; Alleles; Antibodies; Antigens; Ascaridil; Australia; Back; Binding; Biological Assay; Blood specimen; CD4 Positive T Lymphocytes; CD8-Positive T-Lymphocytes; CD8B1 gene; Cell Separation; Cells; Cercopithecus tantalus; Characteristics; Charge; Coculture Techniques; Collaborations; Communicable Diseases; Computer Retrieval of Information on Scientific Projects Database; Consult; Consultations; Custom; Data; Data Analyses; Detection; Development; Diagnostic tests; Epitopes; Extramural Activities; Flow Cytometry; Funding; Gagging; Generations; Genetic; Grant; HIV Antibodies; HIV-1; HLA-B 2705 antigen; Histocompatibility; Histocompatibility Antigens Class I; Hour; Human; Immune response; Immunogenetics; Immunologic Deficiency Syndromes; Immunology; In Situ; Income; Infection; Institution; Laboratories; Leukocytes; Lymphoid Tissue; MHC Class I Genes; MHC Class II Genes; Macaca; Macaca mulatta; Manuscripts; Membrane; Messenger RNA; Methods; Mission; Molecular Biology; Mutagenesis; Mutation; National Cancer Institute; New England; Pathology; Peptides; Pluripotent Stem Cells; Population; Price; Primates; Printing; Process; Production; Protocols documentation; RNA Interference; Recombinants; Reporter; Research; Research Personnel; Resource Allocation; Resources; Reverse Transcriptase Polymerase Chain Reaction; SIV; Sampling; Schools; Science; Serum; Services; Shipping; Ships; Shivering; Silent Mutation; Site-Directed Mutagenesis; Sorting - Cell Movement; Source; Speed; Spices; Staining method; Stains; System; T cell response; T-Lymphocyte; T-Lymphocyte Epitopes; Techniques; Testing; Training; Transgenes; Translations; United States National Institutes of Health; Vaccinated; Vaccination; Vaccines; Variant; Vial device; Viral; Viral load measurement; Virus; Virus Replication; Work; Yellow Fever; Yellow Fever Vaccine; bean; cytokine; data acquisition; design; fast protein liquid chromatography; fitness; induced pluripotent stem cell; instrument; interest; macrophage; member; monocyte; mutant; neutralizing monoclonal antibodies; nonhuman primate; novel; peripheral blood; progenitor; reagent testing; research study; response; simian human immunodeficiency virus; vector; virology

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Objective: To provide expert support to AIDS research conducted at the Primate Center. 1. PROGRESS AND CONCERNS: The Virology Services Unit (VS) performed over 1,700 SIV virus load determinations in FY2009. This is fewer than in FY2008, as our core users pared back on the scope of their studies. We anticipate increased demand in FY2010 as established users are funded to perform more and larger experiments. In anticipation of this increased demand, we tested a new workflow using the high-throughput Roche LightCycler 480 quantitative PCR platform in February 2010. Transition to this workflow will facilitate an expansion of our services and will simplify batch processing of samples as we now charge all users, both intra- and extramural, for virus load determinations. Our chargeback system for extramural investigators had 2 users and generated revenues of $18,255. VS also produced over 4,000 vials of high-titer SIVmac239 stock and 3 custom SIV mutants for WNPRC investigators. In response to investigators interested in evaluating the fitness of multiple mutant strains of SIV, we deployed a "barcode virus" reporter system. We used site-directed mutagenesis to insert a genetic "barcode" of silent mutations into the region of SIVmac239 gag targeted by our standard QRT-PCR assay. These mutations do not affect virus fitness, but they abrogate detection using the primers and probes of our standard assay. This "barcode" virus thus provides a standard against which any viral variant can be directly compared in competing coculture assays. The Tetramer Core of Immunology Services Unit (IS) produced approximately 99,000 tetramer tests in 2009. 25,508 tests were shipped to ten different investigators at nine different institutions, bringing in $76,524 in chargeback income. We also distributed 7,155 tests to laboratories on campus, including the David H. O'Connor laboratory in Pathology, the Thomas Friedrich laboratory at the Vet School and the Watkins Laboratory in Pathology. All three of these labs are also part of the WNPRC. Our FPLC instruments were also utilized by non-primate center investigators, assisting them in preliminary studies, or when their FPLC was not working. We are currently pursuing MHC class II tetramers, and expect to produce our first tetramers in early 2010. We have expanded the alleles that are available for tetramer production in 2009, to include several cynomolgus alleles. We will continue expanding our allele availability in 2010, as more and more cyno and rhesus alleles are found to be important in SIV studies. In addition, we are developing Elisas for class II tetramers, as well as a diagnostic test for peptide binding. Our group makes all of the p27 antibody used by our lab, and also shipped 200 tests of this reagent to Stephen Kent's lab in Australia. For extramural investigators more than 1200 blood samples were processed and shipped out, and 1680 IFN-¿ Elispot tests and 327 intracellular cytokine staining tests were performed. IS also provides expert support to Primate Center, UW-Madison and extramural investigators wishing to use our flow cytometry facilities. More than 2,500 hours were used for flow data acquisition during this year. These activities together resulted in an additional ~$55,000 in chargebacks. In 2009 we purchased a new custom-made BD-LSR II machine to expand our services. We have established or supported the development of several multicolor staining protocols. These included staining panels to test different functional capabilities of antigen specific T cell populations, and panels that identify innate immune responses after yellow fever vaccination. To promote better data analysis in flow cytometry we have introduced the use of Pestle and Spice data analysis softwares. To expand our services with BL-3 level sorting capabilities Dr Rakasz will be trained to operate a FACSAria high speed cell sorter in February. She will have access to a BL-3 level sorting facility on campus and will perform cell sort for investigators who has this request. 2. ALLOCATION OF RESOURCE ACCESS: The central mission of IVS is to provide expert support to AIDS and infectious disease related research conducted at the Primate Center by WNPRC or outside investigators. In fiscal 2009 IS served 9 on-campus and 15 off-campus laboratories, which were funded by both federal and non-federal grants. VS supported 4 on-campus and 2 off-campus users in FY2009. 3. DISSEMINATION: Drs. Friedrich, Wilson and Rakasz, the PIs of VS and IS units, consult closely with users of the service, helping to design experiments and interpret results. We request that projects utilizing Virology and Immunology Services acknowledge the service in manuscripts and presentations. 4. TRAINING: Dr. Friedrich consults regularly with recognized leaders in SIV virology and molecular biology to develop and refine our techniques. For example, custom SIV mutagenesis methods were developed in collaboration with Dr. Ronald Desrosiers at the New England Primate Center. Quantitative RT-PCR techniques were developed in consultation with Dr. Jeffrey Lifson at the National Cancer Institute. IS staff have been trained in flow cytometry techniques at Beckton Dickinson. Dr Rakasz and Ms Kim Weisgrau, members of the flow cytometry facility regularly train new investigators to acquire their data independently on the flow machines at their disposal. PUBLICATIONS: Bonaldo MC, Martins MA, Rudersdorf R, Mudd PA, Sacha JB, Piaskowski SM, Costa Neves PC, Veloso de Santana MG, Vojnov L, Capuano S 3rd, Rakasz EG, Wilson NA, Fulkerson J, Sadoff JC, Watkins DI, Galler R. Recombinant Yellow Fever Vaccine Virus 17D Expressing SIVmac239 Gag Induces SIV-Specific CD8+ T Cell Responses in Rhesus Macaques. J Virol. 2010 Jan 20. [Epub ahead of print] PMID: 20089645 Maness NJ, Wilson NA, Reed JS, Piaskowski SM, Sacha JB, Walsh AD, Thoryk E, Heidecker GJ, Citron MP, Liang X, Bett AJ, Casimiro DR, Watkins DI. Robust, vaccine-induced CD8(+) T lymphocyte response against an out-of-frame epitope. J Immunol. 2010 Jan 1;184(1):67-72. PMID: 19949108 Hessell AJ, Rakasz EG, Tehrani DM, Huber M, Weisgrau KL, Landucci G, Forthal DN, Koff WC, Poignard P, Watkins DI, Burton DR. Broadly neutralizing monoclonal antibodies 2F5 and 4E10 directed against the human immunodeficiency virus type 1 gp41 membrane-proximal external region protect against mucosal challenge by simian-human immunodeficiency virus SHIVBa-L. J Virol. 2010 Feb;84(3):1302-13..PMID: 19906907 Vojnov L, Reed JS, Weisgrau KL, Rakasz EG, Loffredo JT, Piaskowski SM, Sacha JB, Kolar HL, Wilson NA, Johnson RP, Watkins DI. Effective simian immunodeficiency virus-specifici CD8+ T cells lack an easily detectable, shared characteristic. J Virol. 2010 Jan;84(2):753-64. PMID: 19889785 Valentine LE, Loffredo JT, Bean AT, Le¿n EJ, MacNair CE, Beal DR, Piaskowski SM, Klimentidis YC, Lank SM, Wiseman RW, Weinfurter JT, May GE, Rakasz EG, Wilson NA, Friedrich TC, O'Connor DH, Allison DB, Watkins DI. Infection with "escaped" virus variants impairs control of simian immunodeficiency virus SIVmac239 replication in Mamu-B*08-positive macaques. J Virol. 2009 Nov;83(22):11514-27. PMID: 19726517 Maness NJ, Sacha JB, Piaskowski SM, Weisgrau KL, Rakasz EG, May GE, Buechler MB, Walsh AD, Wilson NA, Watkins DI. Novel translation products from simian immunodeficiency virus SIVmac239 Env-encoding mRNA contain both Rev and cryptic T-cell epitopes. J Virol. 2009 Oct;83(19):10280-5. PMID: 19605480 Loffredo JT, Sidney J, Bean AT, Beal DR, Bardet W, Wahl A, Hawkins OE, Piaskowski S, Wilson NA, Hildebrand WH, Watkins DI, Sette A. Two MHC class I molecules associated with elite control of immunodeficiency virus replication, Mamu-B*08 and HLA-B*2705, bind peptides with sequence similarity. J Immunol. 2009 Jun 15;182(12):7763-75.PMID: 19494300. Sacha JB, Giraldo-Vela JP, Buechler MB, Martins MA, Maness NJ, Chung C, Wallace LT, Le¿n EJ, Friedrich TC, Wilson NA, Hiraoka A, Watkins DI. Gag- and Nef-specific CD4+ T cells recognize and inhibit SIV replication in infected macrophages early after infection. Proc Natl Acad Sci U S A. 2009 Jun 16;106(24):9791-6. PMID: 19478057 Hessell AJ, Rakasz EG, Poignard P, Hangartner L, Landucci G, Forthal DN, Koff WC, Watkins DI, Burton DR. Broadly neutralizing human anti-HIV antibody 2G12 is effective in protection against mucosal SHIV challenge even at low serum neutralizing titers. PLoS Pathog. 2009 May;5(5):e1000433. PMID: 19436712 Wilson NA, Keele BF, Reed JS, Piaskowski SM, MacNair CE, Bett AJ, Liang X, Wang F, Thoryk E, Heidecker GJ, Citron MP, Huang L, Lin J, Vitelli S, Ahn CD, Kaizu M, Maness NJ, Reynolds MR, Friedrich TC, Loffredo JT, Rakasz EG, Erickson S, Allison DB, Piatak M Jr, Lifson JD, Shiver JW, Casimiro DR, Shaw GM, Hahn BH, Watkins DI. Vaccine-induced cellular responses control simian immunodeficiency virus replication after heterologous challenge. J Virol. 2009 Jul;83(13):6508-21. PMID: 19403685 Greene JM, Lhost JJ, Burwitz BJ, Budde ML, Macnair CE, Weiker MK, Gostick E, Friedrich TC, Broman KW, Price DA, O'Connor S, O'Connor DH. Extra-lymphoid tissue-resident CD8+ T cells from SIVmac239Deltanef-vaccinated macaques suppress SIVmac239 replication ex vivo. J Virol. 2010 Jan 20. Burwitz BJ, Pendley CJ, Greene JM, Detmer AM, Lhost JJ, Karl JA, Piaskowski SM, Rudersdorf RA, Wallace LT, Bimber BN, Loffredo JT, Cox DG, Bardet W, Hildebrand W, Wiseman RW, O'Connor SL, O'Connor DH. Mauritian cynomolgus macaques share two exceptionally common major histocompatibility complec class I alleles that restrict simian immunodeficiency virus specific CD8+ T cells. J Virol. 2009 Jun;83(12):6011-9. PMID: 19339351 Choi KD, Vodyanik MA, Slukvin II. Generation of mature human myelomonocytic cells through expansion and differentiation of pluripotent stem cell-derived lin-CD34+CD43+CD45+ progenitors. J Clin Invest. Yu J, Hu K, Smuga-Otto K, Tian S, Stewart R, Slukvin II, Thomson JA. Human induced pluripotent stem cells free of vector and transgene sequences. Science. 2009 May 8;324(5928):797-801. PMID: 19325077 Rozner AE, Dambaeva SV, Drenzek JG, Durning M, Golos TG.Generation of macrophages from peripheral blood monocytes in the rhesus monkey. J Immunol Methods. 2009 Dec 31;351(1-2):36-40. PMID: 19818793 Bondarenko GI, Dambaeva SV, Grendell RL, Hughes AL, Durning M, Garthwaite MA, Golos TG. Characterization of cynomolgus and vervet monkey placental MHC class I expression: diversity of the nonhuman primate AG locus. Immunogenetics. 2009 Jun;61(6):431-42. PMID: 19468726 Dambaeva SV, Breburda EE, Durning M, Garthwaite MA, Golos TG. Characterization of decidual leukocyte populations in cynomolgus and vervet monkeys. J Reprod Immunol. 2009 Jun;80(1-2):57-69. PMID: 19398130 Drenzek JG, Vidiguriene J, Vidiguris G, Grendell RL, Dambaeva SV, Durning M, Golos TG. Suppression of Mamu-AG by RNA interference. Am J Reprod Immunol. 2009 Apr 22. PMID: 19392979 Li Q, Skinner PJ, Duan L, Haase AT. A technique to simultaneously visualize virus-specific CD8+ T cells and virus-infected cells in situ. J Vis Exp. 2009 Aug 13;(30). pii: 1561. doi: 10.3791/1561. Salisch NC, Kaufmann DE, Awad AS, Reeves RK, Tighe DP, Li Y, Piatak M Jr, Lifson JD, Evans DT, Pereyra F, Freeman GJ, Johnson RP. Inhibitory TCR coreceptor PD-1 is a sensitive indicator of low-level replication of SIV and HIV-1. J Immunol. 2010 Jan 1;184(1):476-87.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以出现在其他 CRISP 条目中 列出的机构是。 中心，不一定是研究者的机构。 目标：为灵长类动物中心进行的艾滋病研究提供专家支持。 1. 进展和担忧： 病毒学服务部门 (VS) 在 2009 财年进行了 1,700 多个 SIV 病毒载量测定，这比 2008 财年要少，因为我们的核心用户缩减了研究范围，因为现有用户有资金进行执行，因此我们预计 2010 财年的需求会增加。考虑到这种需求的增加，我们于 2010 年 2 月使用高通量 Roche LightCycler 480 定量 PCR 平台测试了新的工作流程。过渡到此工作流程将有助于扩展我们的服务，并简化样本的批处理，因为我们现在向所有用户（包括校内和校外）收取病毒载量测定费用，我们的校外调查人员退款系统有 2 个用户，产生了 18,255 美元的收入。 。 VS 还为 WNPRC 研究人员生产了 4,000 多瓶高滴度 SIVmac239 库存和 3 个定制 SIV 突变体。为了响应有兴趣评估 SIV 多个突变株的适应性的研究人员，我们部署了“条形码病毒”报告系统。 -定向诱变，将沉默突变的遗传“条形码”插入到我们的标准 QRT-PCR 检测所针对的 SIVmac239 gag 区域中。这些突变不会影响病毒适应性。但他们废除了使用我们标准测定的引物和探针进行的检测，因此这种“条形码”病毒提供了一个标准，可以在竞争性共培养测定中直接比较任何病毒变体。 免疫学服务部 (IS) 的四聚体核心在 2009 年生产了大约 99,000 个四聚体测试。25,508 个测试被运送给 9 个不同机构的 10 个不同的研究人员，带来了 76,524 美元的退款收入。我们还向校园实验室分发了 7,155 个测试，包括实验室。 David H. O'Connor 病理学实验室、兽医学院 Thomas Friedrich 实验室和沃特金斯实验室所有这三个实验室也是 WNPRC 的一部分，非灵长类中心研究人员也使用我们的 FPLC 仪器，协助他们进行初步研究，或者当我们目前正在研究 MHC II 类四聚体时。预计在 2010 年初生产出我们的第一个四聚体。我们已在 2009 年扩大了可用于四聚体生产的等位基因，其中包括几个食蟹猴等位基因。 2010 年，随着越来越多的食蟹猴和恒河猴等位基因被发现在 SIV 研究中发挥重要作用，我们正在开发 II 类四聚体的 Elisas，以及肽结合的诊断测试。我们实验室使用的p27抗体，并将该试剂的200个测试运送到澳大利亚的Stephen Kent实验室。 对于校外研究人员来说，处理并运送了超过 1200 份血液样本，以及 1680 份 IFN-¿今年，IS 还为灵长类动物中心、威斯康星大学麦迪逊分校和校外研究人员进行了 Elispot 测试和 327 项细胞内细胞因子染色测试，用于流式数据采集。总共导致额外约 55,000 美元的退款。 2009 年，我们购买了一台新的定制 BD-LSR II 机器来扩展我们的服务，我们已经建立或支持开发了多种多色染色方案，其中包括用于测试抗原特异性 T 细胞群的不同功能能力的染色组。识别黄热病疫苗接种后的先天免疫反应。 为了促进流式细胞术中更好的数据分析，我们引入了 Pestle 和 Spice 数据分析软件的使用。 为了通过 BL-3 级分选能力扩展我们的服务，Rakasz 博士将于 2 月份接受操作 FACSAria 高速细胞分选机的培训，她将可以使用校园内的 BL-3 级分选设施，并为有能力的研究人员进行细胞分选。这个请求。 2. 资源访问的分配： IVS 的核心任务是为 WNPRC 或外部研究人员在灵长类动物中心进行的艾滋病和传染病相关研究提供专家支持。 2009 财年，IS 为 9 个校内实验室和 15 个校外实验室提供服务，这些实验室均由联邦资助。 VS 在 2009 财年支持了 4 名校内用户和 2 名校外用户。 3. 传播： VS 和 IS 单位的 PI 弗里德里希 (Friedrich)、威尔逊 (Wilson) 和拉卡斯 (Rakasz) 博士与该服务的用户密切协商，帮助设计实验和解释结果。我们要求使用病毒学和免疫学服务项目的人在手稿和演示文稿中承认该服务。 4. 培训： Friedrich 博士定期咨询 SIV 病毒学和分子生物学领域的知名领导者，以开发和完善我们的技术。例如，与新英格兰灵长类动物中心的 Ronald Desrosiers 博士合作开发了定制的 SIV 诱变方法。 IS 工作人员在与国家癌症研究所的 Jeffrey Lifson 博士协商后开发，并在该流程的成员 Rakasz 博士和 Kim Weisgrau 女士接受了流式细胞术技术培训。细胞计数设施定期培训新的研究人员，以在他们所使用的流式机器上独立获取数据。 出版物： Bonaldo MC、Martins MA、Rudersdorf R、Mudd PA、Sacha JB、Piaskowski SM、Costa Neves PC、Veloso de Santana MG、Vojnov L、Capuano S 3rd、Rakasz EG、Wilson NA、Fulkerson J、Sadoff JC、Watkins DI、Galler R. 表达 SIVmac239 Gag 的重组黄热病疫苗病毒 17D恒河猴中的 SIV 特异性 CD8+ T 细胞反应。 J Virol，2010 年 1 月 20 日。[印刷前电子版] PMID：20089645 Maness NJ、Wilson NA、Reed JS、Piaskowski SM、Sacha JB、Walsh AD、Thoryk E、Heidecker GJ、Citron MP、Liang X、Bett AJ、Casimiro DR、Watkins DI 稳健的疫苗诱导 CD8(+) T 淋巴细胞。针对框架外表位的反应。《免疫学杂志》2010 年 1 月 1 日；184(1)：67-72。 PMID：19949108 Hessel AJ、Rakasz EG、Tehrani DM、Huber M、Weisgrau KL、Landucci G、Forthal DN、Koff WC、Poignard P、Watkins DI、Burton DR 针对人类免疫缺陷病毒 1 型 gp41 膜的广泛中和单克隆抗体 2F5 和 4E10。 -近端外部区域可防止猿猴对粘膜的攻击免疫缺陷病毒 SHIVBa-L。2010 年 2 月；84(3):1302-13..PMID：19906907 Vojnov L、Reed JS、Weisgrau KL、Rakasz EG、Loffredo JT、Piaskowski SM、Sacha JB、Kolar HL、Wilson NA、Johnson RP、Watkins DI。有效的猴免疫缺陷病毒特异性 CD8+ T 细胞缺乏易于检测的共同特征。 J Virol，2010 年 1 月；84(2)：753-64。 19889785 瓦伦丁 LE、洛弗雷多 JT、比恩 AT、Le¿ n EJ、MacNair CE、Beal DR、Piaskowski SM、Klimentidis YC、Lank SM、Wiseman RW、Weinfurter JT、May GE、Rakasz EG、Wilson NA、Friedrich TC、O'Connor DH、Allison DB、Watkins DI。 “逃逸”病毒变种损害了猿猴免疫缺陷病毒 SIVmac239 复制的控制Mamu-B*08 阳性猕猴。2009 年 11 月；83(22)：11514-27。 Maness NJ、Sacha JB、Piaskowski SM、Weisgrau KL、Rakasz EG、May GE、Buechler MB、Walsh AD、Wilson NA、Watkins DI 来自猿猴免疫缺陷病毒 SIVmac239 Env 编码 mRNA 的新型翻译产物包含 Rev 和隐性 T 细胞。表位。2009 年 10 月；83(19)：10280-5。 PMID：19605480 Loffredo JT、Sidney J、Bean AT、Beal DR、Bardet W、Wahl A、Hawkins OE、Piaskowski S、Wilson NA、Hildebrand WH、Watkins DI、Sette A。两种与免疫缺陷病毒复制的精英控制相关的 MHC I 类分子， Mamu-B*08 和 HLA-B*2705 结合具有序列相似性的肽，2009 年 6 月。 15;182(12):7763-75.PMID:19494300。 Sacha JB、Giraldo-Vela JP、Buechler MB、Martins MA、Maness NJ、Chung C、Wallace LT、Le¿ n EJ、Friedrich TC、Wilson NA、Hiraoka A、Watkins DI。Gag 和 Nef 特异性 CD4+ T 细胞在感染后早期识别并抑制受感染巨噬细胞中的 SIV 复制。2009 年 6 月 16 日；106(24) ）：9791-6。PMID：19478057 Hessel AJ、Rakasz EG、Poignard P、Hangartner L、Landucci G、Forthal DN、Koff WC、Watkins DI、Burton DR。即使在低血清中和滴度下，广泛中和的人抗 HIV 抗体 2G12 也能有效防止粘膜 SHIV 攻击。 PLoS Pathog。2009 年 5 月；5(5)：e1000433。 19436712 Wilson NA、Keele BF、Reed JS、Piaskowski SM、MacNair CE、Bett AJ、Liang X、Wang F、Thoryk E、Heidecker GJ、Citron MP、Huang L、Lin J、Vitelli S、Ahn CD、Kaizu M、Maness NJ , 雷诺兹 MR, 弗里德里希 TC, 洛弗雷多 JT, 拉卡斯 EG, 埃里克森 S, 艾里森 DB, 皮亚塔克 M Jr, Lifson JD、Shiver JW、Casimiro DR、Shaw GM、Hahn BH、Watkins DI。异源攻击后疫苗诱导的细胞反应控制猿猴免疫缺陷病毒的复制。2009 年 7 月；83(13)：6508-21。 Greene JM、Lhost JJ、Burwitz BJ、Budde ML、Macnair CE、Weiker MK、Gostick E、Friedrich TC、Broman KW、Price DA、O'Connor S、O'Connor DH 来自淋巴组织外的 CD8+ T 细胞。接种 SIVmac239Deltanef 的猕猴可抑制 SIVmac239 体外复制，2010 年 1 月 J Virol。 20. 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