Virus growth and antibody responses following respiratory tract infection of ferrets and mice with WT and P/V mutants of the paramyxovirus Simian Virus 5.
Virus growth and antibody responses following respiratory tract infection of ferrets and mice with WT and P/V mutants of the paramyxovirus Simian Virus 5.
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DOI：
10.1016/j.virol.2008.03.034
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发表时间：
2008-07-05
期刊：
影响因子：
3.7
通讯作者：
Parks, Griffith D.
中科院分区：
文献类型：
--
作者：
Capraro, Gerald A.;Johnson, John B.;Kock, Nancy D.;Parks, Griffith D.
P/V基因取代将非致细胞病变副粘病毒猿猴病毒5（SV 5）（在人类组织培养细胞中是宿主细胞反应的不良诱导剂）转化为突变体（P/V-CPI−），诱导高水平的细胞凋亡、干扰素（IFN）-β和促炎细胞因子。然而，SV 5-P/V基因突变对病毒生长和动物适应性免疫应答的影响尚未确定。在这里，我们使用了两个不同的动物模型系统来测试这一假设，即SV 5-P/V突变体是组织培养中先天性应答的更有效的激活剂，也将引起更高的抗病毒抗体应答。在小鼠细胞中，体外研究确定了一组SV 5-P/V突变体，其限制IFN应答的能力范围不等。用这些WT和P/V突变病毒鼻内感染小鼠，在所有测试剂量下均引起等效的抗SV 5 IgG应答，并且从呼吸道回收的病毒滴度不可区分。在雪貂肺成纤维细胞的原代培养物中，WT rSV 5和P/V-CPI−病毒的表型与在人类细胞系中建立的表型相似，包括IFN分泌、IFN信号传导和细胞凋亡的差异诱导。与P/V-CPI−突变体相比，用低剂量WT rSV 5鼻内感染雪貂引起的抗SV 5血清IgG应答高约500倍，这与气管组织中WT病毒的总体较高病毒滴度相关。雪貂感染P/V-CPI−后，抗体应答呈剂量依赖性增加，而感染WT rSV 5后则无此现象。总之，我们的数据表明，WT rSV 5和P/V突变体可以引起不同的先天性和适应性免疫表型的雪貂动物模型系统，但不是在小鼠系统。我们提出了一个模型的P/V基因置换对SV 5的生长和免疫反应在体内的影响。
P/V gene substitutions convert the non-cytopathic paramyxovirus Simian Virus 5 (SV5), which is a poor inducer of host cell responses in human tissue culture cells, into a mutant (P/V-CPI−) that induces high levels of apoptosis, interferon (IFN)-beta, and proinflammatory cytokines. However, the effect of SV5-P/V gene mutations on virus growth and adaptive immune responses in animals has not been determined. Here, we used two distinct animal model systems to test the hypothesis that SV5-P/V mutants which are more potent activators of innate responses in tissue culture will also elicit higher antiviral antibody responses. In mouse cells, in vitro studies identified a panel of SV5-P/V mutants that ranged in their ability to limit IFN responses. Intranasal infection of mice with these WT and P/V mutant viruses elicited equivalent anti-SV5 IgG responses at all doses tested, and viral titers recovered from the respiratory tract were indistinguishable. In primary cultures of ferret lung fibroblasts, WT rSV5 and P/V-CPI− viruses had phenotypes similar to those established in human cell lines, including differential induction of IFN secretion, IFN signaling and apoptosis. Intranasal infection of ferrets with a low dose of WT rSV5 elicited ~ 500 fold higher anti-SV5 serum IgG responses compared to the P/V-CPI− mutant, and this correlated with overall higher viral titers for the WT virus in tracheal tissues. There was a dose-dependent increase in antibody response to infection of ferrets with P/V-CPI−, but not with WT rSV5. Together our data indicate that WT rSV5 and P/V mutants can elicit distinct innate and adaptive immunity phenotypes in the ferret animal model system, but not in the mouse system. We present a model for the effect of P/V gene substitutions on SV5 growth and immune responses in vivo.
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影响因子：
3.7
作者：
Arimilli, Subhashini;Johnson, John B.;Parks, Griffith D.
通讯作者：
Parks, Griffith D.
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