Ahi Yadvinder S, Vemula Sai V, Hassan Ahmed O, Costakes Greg, Stauffacher Cynthia, Mittal Suresh K
Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University West Lafayette, IN, USA ; Purdue University Center for Cancer Research, Purdue University West Lafayette, IN, USA ; Bindley Bioscience Center, Purdue University West Lafayette, IN, USA.
Purdue University Center for Cancer Research, Purdue University West Lafayette, IN, USA ; Bindley Bioscience Center, Purdue University West Lafayette, IN, USA ; Department of Biological Sciences, Purdue University West Lafayette, IN, USA.
Front Microbiol. 2015 Apr 21;6:318. doi: 10.3389/fmicb.2015.00318. eCollection 2015.
The mechanism of genome packaging in adenoviruses (AdVs) is presumed to be similar to that of dsDNA viruses including herpesviruses and dsDNA phages. First, the empty capsids are assembled after which the viral genome is pushed through a unique vertex by a motor which consists of three minimal components: an ATPase, a small terminase and a portal. Various components of this motor exist as ring-like structures forming a central channel through which the DNA travels during packaging. In AdV, the IVa2 protein is believed to function as a packaging ATPase, however, the equivalents of the small terminase and the portal have not been identified in AdVs. IVa2 interacts with another viral protein late region 4 (L4) 33K which is important for genome packaging. Both IVa2 and 33K are expressed at high levels during the late stage of virus infection. The oligomeric state of IVa2 and 33K was analyzed in virus-infected cells, IVa2 and 33K transfected cells, AdV particles, or as recombinant purified proteins. Electron microscopy of the purified proteins showed ring-like oligomers for both proteins which is consistent with their putative roles as a part of the packaging motor. We found that the ATPase activity of IVa2 is stimulated in the presence of 33K and the AdV genome. Our results suggest that the 33K functions analogous to the small terminase proteins and so will be part of the packaging motor complex.
腺病毒(AdV)的基因组包装机制被认为与包括疱疹病毒和双链DNA噬菌体在内的双链DNA病毒相似。首先,空衣壳组装完成,之后病毒基因组通过一个由三个最小组件组成的马达被推过一个独特的顶点:一个ATP酶、一个小末端酶和一个门户蛋白。这个马达的各种组件以环状结构存在,形成一个中央通道,DNA在包装过程中通过该通道移动。在腺病毒中,IVa2蛋白被认为作为包装ATP酶发挥作用,然而,腺病毒中尚未鉴定出小末端酶和门户蛋白的等效物。IVa2与另一种病毒蛋白晚期区域4(L4)33K相互作用,L4 33K对基因组包装很重要。IVa2和33K在病毒感染后期均高水平表达。在病毒感染细胞、IVa2和33K转染细胞、腺病毒颗粒或作为重组纯化蛋白的情况下,分析了IVa2和33K的寡聚状态。纯化蛋白的电子显微镜观察显示这两种蛋白均为环状寡聚体,这与其作为包装马达一部分的假定作用一致。我们发现,在存在33K和腺病毒基因组的情况下,IVa2的ATP酶活性受到刺激。我们的结果表明,33K的功能类似于小末端酶蛋白,因此将成为包装马达复合体的一部分。