Kara P D, Afonso C L, Wallace D B, Kutish G F, Abolnik C, Lu Z, Vreede F T, Taljaard L C F, Zsak A, Viljoen G J, Rock D L
Biotechnology Division, Onderstepoort Veterinary Institute, Onderstepoort, South Africa.
Arch Virol. 2003 Jul;148(7):1335-56. doi: 10.1007/s00705-003-0102-0.
The genomic sequences of 3 strains of Lumpy skin disease virus (LSDV) (Neethling type) were compared to determine molecular differences, viz. the South African vaccine strain (LW), a virulent field-strain from a recent outbreak in South Africa (LD), and the virulent Kenyan 2490 strain (LK). A comparison between the virulent field isolates indicates that in 29 of the 156 putative genes, only 38 encoded amino acid differences were found, mostly in the variable terminal regions. When the attenuated vaccine strain (LW) was compared with field isolate LD, a total of 438 amino acid substitutions were observed. These were also mainly in the terminal regions, but with notably more frameshifts leading to truncated ORFs as well as deletions and insertions. These modified ORFs encode proteins involved in the regulation of host immune responses, gene expression, DNA repair, host-range specificity and proteins with unassigned functions. We suggest that these differences could lead to restricted immuno-evasive mechanisms and virulence factors present in attenuated LSDV strains. Further studies to determine the functions of the relevant encoded gene products will hopefully confirm this assumption. The molecular design of an improved LSDV vaccine is likely to be based on the strategic manipulation of such genes.
比较了3株结节性皮肤病病毒(LSDV)(内斯林型)的基因组序列,以确定分子差异,即南非疫苗株(LW)、南非近期一次疫情中的强毒野毒株(LD)和强毒肯尼亚2490株(LK)。强毒野毒株之间的比较表明,在156个推定基因中的29个基因中,仅发现38个编码氨基酸差异,主要存在于可变末端区域。当将减毒疫苗株(LW)与野毒株LD进行比较时,共观察到438个氨基酸替换。这些替换也主要位于末端区域,但明显有更多的移码导致截短的开放阅读框以及缺失和插入。这些修饰的开放阅读框编码参与宿主免疫反应调节、基因表达、DNA修复、宿主范围特异性的蛋白质以及功能未明确的蛋白质。我们认为这些差异可能导致减毒LSDV株中存在受限的免疫逃避机制和毒力因子。进一步研究确定相关编码基因产物的功能有望证实这一假设。改进的LSDV疫苗的分子设计可能基于对此类基因的策略性操作。