Shakya Akhalesh K, O'Callaghan Dennis J, Kim Seong K
Department of Microbiology and Immunology, Center for Molecular and Tumor Virology, Louisiana State University Health Sciences Center, Shreveport, LA, United States.
Front Vet Sci. 2017 Dec 11;4:211. doi: 10.3389/fvets.2017.00211. eCollection 2017.
Equine herpesvirus 1 (EHV-1) is a major pathogen affecting equines worldwide. The virus causes respiratory disease, abortion, and, in some cases, neurological disease. EHV-1 Kentucky A (KyA) is attenuated in the mouse and equine, whereas wild-type pathogenic strain RacL11 induces severe inflammatory infiltration of the lung, causing infected mice to succumb. The complete DNA sequencing of the KyA genome revealed that genes UL17 (ORF17), US6 (ORF73; gI), US7 (ORF74; gE), and US8 (ORF75; 10 K) are deleted as compared to the RacL11 and Ab4 genomes. In-frame deletions in the US1 (ORF68), US4 (ORF71; gp2), and UL63 (ORF63; EICP0) genes and point mutations in 14 different open reading frames (ORFs) were detected in the KyA genome. Interestingly, UL1 (ORF1) and UL2 (ORF2) were deleted in both KyA and RacL11. Our previous studies showed that EHV-1 glycoproteins gI, gE, and full-length gp2 contribute to the pathogenesis of the RacL11 strain. The confirmation of these gene deletions in KyA suggests their contribution to the attenuation of this virus. The growth kinetics results revealed that KyA replicates to high titers in cell culture as compared to RacL11 and Ab4, indicating that the above genomic deletions and mutations in KyA do not have an inhibitory effect on KyA replication in cells of mouse, rabbit, equine, or human origin. Studies of EHV-1 pathogenesis in CBA mice showed that KyA is attenuated whereas mice infected with RacL11 succumbed by 3-6 days post-infection, which is consistent with our previous results.
马疱疹病毒1型（EHV-1）是一种影响全球马匹的主要病原体。该病毒可引发呼吸道疾病、流产，在某些情况下还会导致神经疾病。EHV-1肯塔基A株（KyA）在小鼠和马体内具有减毒特性，而野生型致病菌株RacL11会引发肺部严重的炎症浸润，导致感染小鼠死亡。KyA基因组的全DNA测序显示，与RacL11和Ab4基因组相比，基因UL17（ORF17）、US6（ORF73；gI）、US7（ORF74；gE）和US8（ORF75；10K）缺失。在KyA基因组中检测到US1（ORF68）、US4（ORF71；gp2）和UL63（ORF63；EICP0）基因的框内缺失以及14个不同开放阅读框（ORF）中的点突变。有趣的是，KyA和RacL11中均缺失了UL1（ORF1）和UL2（ORF2）。我们之前的研究表明，EHV-1糖蛋白gI、gE和全长gp2与RacL11菌株发病机制有关。在KyA中证实这些基因缺失表明它们对该病毒的减毒作用。生长动力学结果显示，与RacL11和Ab4相比，KyA在细胞培养中可复制至较高滴度，这表明KyA中上述基因组缺失和突变对其在小鼠、兔子、马或人源细胞中的复制没有抑制作用。对CBA小鼠中EHV-1发病机制的研究表明，KyA具有减毒作用，而感染RacL11的小鼠在感染后3至6天死亡，这与我们之前的结果一致。
