van Santen Vicky L, Toro Haroldo
Department of Pathobiology, 264 Greene Hall, College of Veterinary Medicine, Auburn University, Auburn, AL 36849-5519, USA.
Avian Pathol. 2008 Jun;37(3):293-306. doi: 10.1080/03079450802043783.
We examined spike (S) gene sequences of the virus populations of four different commercial ArkDPI-derived infectious bronchitis coronavirus vaccines before and during a single passage in specific pathogen free chickens. We found different degrees of genetic heterogeneity among the four vaccines before passage in chickens, ranging from no apparent heterogeneity to heterogeneity in 20 positions in the S gene. In all except one position, nucleotide differences were non-synonymous. The majority of amino acid differences were in the S1 subunit of the protein. For three of the four ArkDPI-derived vaccines, a single subpopulation with an S gene sequence distinct from the vaccine majority consensus at 5 to 11 codons was selected in chickens within 3 days after ocular vaccination. In contrast, we obtained no evidence for selection of specific subpopulations of the fourth ArkDPI-derived vaccine or Massachusetts or DE072 serotype vaccines. The virus subpopulations within each vaccine selected by chickens are similar in their S1 gene sequences, but distinct in the 3' portion of the S2 subunit gene for each of the three vaccines. In the S1 gene, the selected subpopulations are more similar to the virulent parental ArkDPI isolate than to the predominant vaccine population. The different proportions of distinct subpopulations in Ark vaccines apparently more fit for replication in the respiratory tract of chickens might cause different degrees of damage to respiratory epithelium and/or immune responses in vaccinated chickens. Sequence comparisons provided no evidence to support that ArkDPI-like field isolates were derived directly from host-selected vaccine virus subpopulations.
我们检测了四种不同的源自ArkDPI的商业传染性支气管炎冠状病毒疫苗在无特定病原体鸡群单次传代之前及传代过程中的病毒群体的刺突(S)基因序列。我们发现这四种疫苗在鸡群传代之前存在不同程度的遗传异质性,范围从无明显异质性到S基因中有20个位置存在异质性。除一个位置外,所有核苷酸差异均为非同义突变。大多数氨基酸差异存在于该蛋白的S1亚基中。对于四种源自ArkDPI的疫苗中的三种,在眼内接种后3天内,鸡群中选择出了一个S基因序列与疫苗多数共识在5至11个密码子处不同的单一亚群。相比之下,我们没有获得证据表明第四种源自ArkDPI的疫苗或马萨诸塞州或DE072血清型疫苗存在特定亚群的选择。鸡群选择的每种疫苗中的病毒亚群在其S1基因序列上相似,但三种疫苗各自在S2亚基基因的3'部分不同。在S1基因中,所选亚群与强毒株亲本ArkDPI分离株比与主要疫苗群体更相似。Ark疫苗中不同比例的不同亚群显然更适合在鸡的呼吸道中复制,这可能会对接种疫苗的鸡的呼吸道上皮和/或免疫反应造成不同程度的损害。序列比较没有提供证据支持类似ArkDPI的田间分离株直接源自宿主选择的疫苗病毒亚群。