Desmarets Lowiese M B, Vermeulen Ben L, Theuns Sebastiaan, Conceição-Neto Nádia, Zeller Mark, Roukaerts Inge D M, Acar Delphine D, Olyslaegers Dominique A J, Van Ranst Marc, Matthijnssens Jelle, Nauwynck Hans J
Department of Virology, Parasitology and Immunology, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, B-9820 Merelbeke, Belgium.
Laboratory of Clinical Virology, Department of Microbiology and Immunology, Rega Institute for Medical Research, Minderbroedersstraat 10, B-3000 Leuven, Belgium.
Sci Rep. 2016 Jan 29;6:20022. doi: 10.1038/srep20022.
Feline infectious peritonitis (FIP) results from mutations in the viral genome during a common feline enteric coronavirus (FECV) infection. Since many virological and immunological data on FECV infections are lacking, the present study investigated these missing links during experimental infection of three SPF cats with FECV strain UCD. Two cats showed mild clinical signs, faecal shedding of infectious virus from 4 dpi, a cell-associated viraemia at inconsistent time points from 5 dpi, a highly neutralising antibody response from 9 dpi, and no major abnormalities in leukocyte numbers. Faecal shedding lasted for 28-56 days, but virus shed during this stage was less infectious in enterocyte cultures and affected by mutations. Remarkably, in the other cat neither clinical signs nor acute shedding were seen, but virus was detected in blood cells from 3 dpi, and shedding of non-enterotropic, mutated viruses suddenly occurred from 14 dpi onwards. Neutralising antibodies arose from 21 dpi. Leukocyte numbers were not different compared to the other cats, except for the CD8(+) regulatory T cells. These data indicate that FECV can infect immune cells even in the absence of intestinal replication and raise the hypothesis that the gradual adaptation to these cells can allow non-enterotropic mutants to arise.
猫传染性腹膜炎(FIP)是由普通猫肠道冠状病毒(FECV)感染期间病毒基因组发生突变所致。由于缺乏许多关于FECV感染的病毒学和免疫学数据,本研究在三只无特定病原体(SPF)猫感染FECV毒株UCD的实验过程中,对这些缺失环节进行了调查。两只猫表现出轻微的临床症状,从感染后第4天开始粪便中排出传染性病毒,从感染后第5天起在不同时间点出现细胞相关病毒血症,从感染后第9天起出现高度中和抗体反应,白细胞数量无重大异常。粪便排毒持续28 - 56天,但在此阶段排出的病毒在肠上皮细胞培养物中的传染性较低且受到突变影响。值得注意的是,在另一只猫中,既未观察到临床症状也未出现急性排毒,但从感染后第3天起在血细胞中检测到病毒,并且从感染后第14天起突然出现非嗜肠性突变病毒的排毒。中和抗体从感染后第21天开始出现。除CD8(+)调节性T细胞外,白细胞数量与其他猫相比无差异。这些数据表明,即使在没有肠道复制的情况下,FECV也能感染免疫细胞,并提出了这样的假设,即对这些细胞的逐渐适应可使非嗜肠性突变体产生。