Olsen L M, Ch'ng T H, Card J P, Enquist L W
Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
J Virol. 2006 Jul;80(13):6387-98. doi: 10.1128/JVI.00352-06.
The pseudorabies virus (PRV) Us3 gene is conserved among the alphaherpesviruses and encodes a serine/threonine protein kinase that is not required for growth in standard cell lines. In this report, we used a compartmented culture system to investigate the role of PRV Us3 in viral replication in neurons, in spread from neurons to PK15 cells, and in axon-mediated spread of infection. We also examined the role of Us3 in neuroinvasion and virulence in rodents. Us3 null mutants produce about 10-fold less infectious virus from neurons than wild-type virus and have no discernible phenotypes for axonal targeting of viral components in cultured peripheral nervous system neurons. After eye infection in rodents, Us3 null mutants were slightly attenuated for virulence, with a delayed onset of symptoms compared to the wild type or a Us3 null revertant. While initially delayed, the symptoms increased in severity until they approximated those of the wild-type virus. Us3 null mutants were neuroinvasive, spreading in both efferent and afferent circuits innervating eye tissues.
伪狂犬病病毒（PRV）的Us3基因在α疱疹病毒中保守，编码一种丝氨酸/苏氨酸蛋白激酶，该激酶在标准细胞系中生长并非必需。在本报告中，我们使用分隔培养系统来研究PRV Us3在神经元中的病毒复制、从神经元向PK15细胞的传播以及轴突介导的感染传播中的作用。我们还研究了Us3在啮齿动物神经侵袭和毒力中的作用。Us3缺失突变体从神经元产生的感染性病毒比野生型病毒少约10倍，并且在培养的外周神经系统神经元中，对于病毒成分的轴突靶向没有明显的表型。在啮齿动物眼部感染后，Us3缺失突变体的毒力略有减弱，与野生型或Us3缺失回复株相比，症状出现延迟。虽然最初有延迟，但症状严重程度增加，直至接近野生型病毒的症状。Us3缺失突变体具有神经侵袭性，可在支配眼组织的传出和传入回路中传播。
