DETERMINANTS OF CHRONIC GAMMAHERPESVIRUS 68 INFECTION

慢性丙型疱疹病毒 68 感染的决定因素

• 批准号: 7349299
• 负责人: James Craig Forrest
• 金额: $ 4.01万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-06-09 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7349299
• 关键词: genes; infection; mutant; role

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. Gammaherpesviruses establish life-long, latent infections in host lymphocytes during which a limited subset of viral genes facilitate viral maintenance. ORF73 is a conserved gammaherpesvirus gene whose product was demonstrated for Kaposi?s sarcoma-associated herpesvirus to tether viral genomes to host chromosomes and interfere with cellular homeostatic regulatory pathways. To understand the role of ORF73 in the establishment and maintenance of ?HV68 latent infection in vivo, we utilized targeted mutants to define ORF73 as critical to the establishment of a latent infection following intranasal inoculation. In addition, ORF73 mutants exhibited a severe replication defect in the lungs of infected mice. Analysis of viral replication in primary murine embryonic fibroblasts revealed that lytic replication of ORF73 mutant virus is impaired in culture. Further, this replication deficit correlates with inhibition of host translation and increased kinetics of apoptosis in infected cells. These findings suggest a role for ORF73 in limiting host-cell death to promote efficient viral replication and dissemination that facilitates the establishment of ?HV68 latent infection.

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。伽马疱疹病毒在宿主淋巴细胞中建立终身的潜伏感染，在此期间，有限的病毒基因亚集有助于病毒的维持。ORF73是一种保守的伽马疱疹病毒基因，其产物被证实可用于卡波西-S肉瘤相关疱疹病毒将病毒基因组与宿主染色体连接，干扰细胞内稳态调节通路。为了了解ORF73在体内建立和维持？HV68潜伏感染中的作用，我们利用靶向突变体将ORF73定义为在鼻腔接种后建立潜伏感染的关键。此外，ORF73突变体在感染小鼠的肺中显示出严重的复制缺陷。病毒在原代小鼠胚胎成纤维细胞中的复制分析表明，ORF73突变病毒的裂解复制在培养中受到损害。此外，这种复制缺陷与宿主翻译的抑制和感染细胞中凋亡动力学的增加有关。这些发现表明，ORF73在限制宿主细胞死亡方面发挥了作用，从而促进了病毒的有效复制和传播，从而促进了？hv68潜伏感染的建立。