POLYOMAVIRUS IN HUMAN RENAL ALLOGRAFT TISSUE

人肾同种异体移植组织中的多瘤病毒

• 批准号: 7601288
• 负责人: PARMJEET S RANDHAWA
• 金额: $ 0.03万
• 依托单位: CARNEGIE-MELLON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-01 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7601288
• 关键词: Acute; Adult; Affect; Allografting; BK Virus; Base Sequence; Biological Assay; Blood; Carcinoma; Chronic; Clinical; Computer Retrieval of Information on Scientific Projects Database; Condition; Cultured Cells; DNA Microarray Chip; DNA Microarray format; DNA Sequence Rearrangement; Development; Distress; Enzyme-Linked Immunosorbent Assay; Functional disorder; Funding; Future; Gene Expression; Gene Mutation; Genitourinary system; Genotype; Grant; Human; Immunosuppressive Agents; In Vitro; Incidence; Infection; Institution; Kidney; Kidney Diseases; Kidney Transplantation; Measures; Medical center; Microarray Analysis; Mycophenolate Mofetil/Tacrolimus; Patients; Pharmaceutical Preparations; Polymerase Chain Reaction; Polyomavirus; Rate; Research; Research Personnel; Resources; Reverse Transcriptase Polymerase Chain Reaction; Risk; Sampling; Simian virus 40; Source; Specimen; Testing; Therapeutic; Tissues; Transplant Recipients; Treatment Protocols; United States National Institutes of Health; Urine; Viral; Viral Genome; Virus; design; falls; kidney allograft; man

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. With the introduction of immunosuppressive drugs such as tacrolimus and mycophenolate mofetil, the incidence of acute rejection in renal transplantation has fallen to <10% at some major medical centers. Unfortunately, these intensive therapeutic regimens increase the risk for vira infections. Of particular concern is the recent emergence of polyomavirus allograft nephropathy (PVAN) in approximately 5% of patients. PVAN is an inadequately studied and distressing condition that frequently leads to graft loss. Since polyomavirus( PV) is latent in the kidney of up to 50% of healthy adults, it is likely that milder forms of PV associated graft dysfunction go unrecognized & untreated, leading to ongoing graft damage and accelerated development of chronic rejection. The specific aims of this proposal are (1) T characterize the complete clinical spectrum of PV infection, (2) To delineate the host & viral factors that affect PV replication in man (3) To analyze PV infection associated cellular gene expression in cultured cells, blood and urine of kidney transplant patients, and tissue specimens with urogenital carcinoma, and (4) To perform in-vitro testing of anti-BK virus drugs for possible future use in the clinical arena. These specific aims will be accomplished by (a) Performing PCR for polyomaviruses BK, JC, and SV40 in clinical samples, (b) Nucleotide sequencing to assign viral genotypes and characterize genetic mutations and rearrangements in the viral genome, (c) Using DNA microarray technology, RT-PCR, & ELISA to characterize virus induced host gene expression, and (d) Testing the effect of putative anti-viral drugs in a flow cytometric assay designed to measure the rate of viral replication i cultured cells.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 随着他克莫司和霉菌酸酯等免疫抑制药物的引入，在某些主要的医疗中心，肾移植中急性排斥的发生率降至<10％。不幸的是，这些密集的治疗方案增加了Vira感染的风险。特别关心的是大约5％的患者最近出现了多瘤病毒同种异体移植肾病（PVAN）。 PVAN是一种经常导致移植物损失的经常研究和令人痛苦的状况。由于多瘤病毒（PV）在多达50％的健康成年人的肾脏中潜在潜在，因此，较温和的PV相关的移植功能障碍的形式可能未经识别和未经治疗，从而导致持续的嫁接损害和加速慢性排斥。该提案的具体目的是（1）T表征PV感染的完整临床谱，（2）描绘了影响人（3）中PV复制的宿主和病毒因子，以分析PV感染在培养的细胞中相关的细胞基因表达，肾脏移植患者的血液和尿液的血液和尿液的尿液，以及与尿素型癌蛋白瘤相结合（4），以及（4），以及（4）。病毒药物，用于临床领域的未来使用。这些具体目标将通过（a）在临床样本中对多瘤病毒BK，JC和SV40进行PCR来实现，（b）核苷酸测序分配病毒基因型，并在病毒基因组中使用DNA MicroArray Technology和Elt-PCR效应（rt-PRCR和ELIS）在病毒基因组中表征遗传突变和重新分组（C）流式细胞仪测定中的假定抗病毒药物，旨在测量病毒复制I培养细胞的速率。