Curanović D, Lyman M G, Bou-Abboud C, Card J P, Enquist L W
Department of Molecular Biology, Princeton University, 314 Schultz Laboratory, Princeton, NJ 08544, USA.
J Virol. 2009 Feb;83(3):1173-83. doi: 10.1128/JVI.02102-08. Epub 2008 Nov 19.
The attenuated pseudorabies virus (PRV) strain Bartha contains several characterized mutations that affect its virulence and ability to spread through neural circuits. This strain contains a small genomic deletion that abrogates anterograde spread and is widely used as a retrograde-restricted neural circuit tracer. Previous studies showed that the retrograde-directed spread of PRV Bartha is slower than that of wild-type PRV. We used compartmented neuronal cultures to characterize the retrograde defect and identify the genetic basis of the phenotype. PRV Bartha is not impaired in retrograde axonal transport, but transneuronal spread among neurons is diminished. Repair of the U(L)21 locus with wild-type sequence restored efficient transneuronal spread both in vitro and in vivo. It is likely that mutations in the Bartha U(L)21 gene confer defects that affect infectious particle production, causing a delay in spread to presynaptic neurons and amplification of infection. These events manifest as slower kinetics of retrograde viral spread in a neural circuit.
减毒伪狂犬病病毒（PRV）巴塔株含有几个已明确的突变，这些突变影响其毒力以及通过神经回路传播的能力。该毒株包含一个小的基因组缺失，此缺失消除了顺行传播，并且被广泛用作逆行限制神经回路示踪剂。先前的研究表明，PRV巴塔株的逆行传播比野生型PRV慢。我们使用分隔式神经元培养来表征逆行缺陷并确定该表型的遗传基础。PRV巴塔株在逆行轴突运输方面没有受损，但神经元之间的跨神经元传播减少。用野生型序列修复U(L)21位点可在体外和体内恢复有效的跨神经元传播。巴塔U(L)21基因中的突变可能导致影响感染性颗粒产生的缺陷，从而导致向突触前神经元传播的延迟和感染的放大。这些事件表现为神经回路中逆行病毒传播的动力学较慢。
