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.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。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。列出的机构适用于该中心，这不一定是调查员的机构。 γ掌病毒在宿主淋巴细胞中建立了终生的潜在感染，在此期间，病毒基因有限的子集有助于病毒维持。 ORF73是一种保守的伽马疱疹病毒基因，其产物用于Kaposi肉瘤相关的疱疹病毒与系链病毒基因组的产物，以宿主染色体并干扰细胞稳态调节途径。为了了解ORF73在体内潜在感染的建立和维持中的作用，我们利用靶向突变体将ORF73定义为对鼻内接种后建立潜在感染至关重要。另外，ORF73突变体在感染小鼠的肺中表现出严重的复制缺陷。对原代鼠胚胎成纤维细胞中病毒复制的分析表明，ORF73突变病毒的裂解复制在培养中受损。此外，这种复制缺陷与受感染细胞中宿主翻译的抑制和凋亡动力学增加有关。这些发现表明ORF73在限制宿主 - 细胞死亡中的作用，以促进有效的病毒复制和传播，从而促进建立？HV68潜在感染。