Repair of the UL21 Locus in Pseudorabies Virus Bartha Enhances the Kinetics of Retrograde, Transneuronal Infection In Vitro and In Vivo
Repair of the UL21 Locus in Pseudorabies Virus Bartha Enhances the Kinetics of Retrograde, Transneuronal Infection In Vitro and In Vivo
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DOI：
10.1128/jvi.02102-08
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发表时间：
2009-02-01
影响因子：
5.4
通讯作者：
Enquist, L. W.
中科院分区：
文献类型：
--
作者：
Curanovic, D.;Lyman, M. G.;Enquist, L. W.
减毒伪狂犬病病毒（PRV）Bartha株包含若干已明确特征的突变，这些突变影响其毒力以及在神经回路中传播的能力。该毒株含有一个小的基因组缺失，这一缺失会阻碍顺行传播，并被广泛用作逆行受限的神经回路示踪剂。先前的研究表明，PRV Bartha的逆行传播比野生型PRV慢。我们利用分隔的神经元培养物来描述逆行缺陷的特征，并确定该表型的遗传基础。PRV Bartha在逆行轴突运输方面没有受损，但其在神经元之间的跨神经元传播减弱。用野生型序列修复U(L)21基因座可在体外和体内恢复有效的跨神经元传播。Bartha的U(L)21基因中的突变很可能导致影响传染性颗粒产生的缺陷，从而造成向突触前神经元传播的延迟以及感染的扩增。这些情况表现为神经回路中病毒逆行传播的动力学变慢。
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.