Marcucci Katherine T, Martina Yuri, Harrison Frank, Wilson Carolyn A, Salomon Daniel R
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
Virology. 2008 Jun 5;375(2):637-45. doi: 10.1016/j.virol.2008.02.017. Epub 2008 Mar 19.
The porcine endogenous retrovirus (PERV) Gag protein contains two late (L) domain motifs, PPPY and P(F/S)AP. Using viral release assays we demonstrate that PPPY is the dominant L domain involved in PERV release. PFAP represents a novel retroviral L domain variant and is defined by abnormal viral assembly phenotypes visualized by electron microscopy and attenuation of early PERV release as measured by viral genomes. PSAP is functionally dominant over PFAP in early PERV release. PSAP virions are 3.5-fold more infectious in vitro by TCID(50) and in vivo results in more RNA positive tissues and higher levels of proviral DNA using our human PERV-A receptor (HuPAR-2) transgenic mouse model [Martina, Y., Marcucci, K.T., Cherqui, S., Szabo, A., Drysdale, T., Srinivisan, U., Wilson, C.A., Patience, C., Salomon, D.R., 2006. Mice transgenic for a human porcine endogenous retrovirus receptor are susceptible to productive viral infection. J. Virol. 80 (7), 3135-3146]. The functional hierarchies displayed by PERV L domains, demonstrates that L domain selection in viral evolution exists to promote efficient viral assembly, release and infectivity in the virus-host context.
猪内源性逆转录病毒（PERV）的Gag蛋白包含两个晚期（L）结构域基序，PPPY和P（F/S）AP。通过病毒释放试验，我们证明PPPY是参与PERV释放的主要L结构域。PFAP代表一种新型逆转录病毒L结构域变体，通过电子显微镜观察到的异常病毒组装表型以及通过病毒基因组测量的早期PERV释放减弱来定义。在早期PERV释放中，PSAP在功能上优于PFAP。使用我们的人PERV-A受体（HuPAR-2）转基因小鼠模型，PSAP病毒颗粒在体外通过TCID（50）的感染性高3.5倍，在体内导致更多的RNA阳性组织和更高水平的前病毒DNA[Martina, Y., Marcucci, K.T., Cherqui, S., Szabo, A., Drysdale, T., Srinivisan, U., Wilson, C.A., Patience, C., Salomon, D.R., 2006. 转人猪内源性逆转录病毒受体基因的小鼠易受生产性病毒感染。《病毒学杂志》80 (7), 3135 - 3146]。PERV L结构域显示的功能层次结构表明，病毒进化中的L结构域选择是为了在病毒-宿主环境中促进有效的病毒组装、释放和感染性。
