Pandey R, Bechtel M K, Su Y, Ghosh A K, Hayes K A, Mathes L E, Roy-Burman P
Department of Pathology, University of Southern California School of Medicine, Los Angeles 90033, USA.
Virology. 1995 Dec 20;214(2):584-92. doi: 10.1006/viro.1995.0069.
This study was initiated to evaluate the in vivo infectivity and pathogenicity of a group of recombinant feline leukemia viruses (rFeLVs) previously generated by in vitro forced recombination between a FeLV subgroup A virus (FeLV-A) and an endogenous FeLV (enFeLV) envelope (env) element (Sheets et al., 1992, Virology 190, 849-855). To determine infectivity of rFeLVs, neonatal cats were inoculated with rFeLVs alone or in combination with FeLV-A. The recombinant viruses were able to replicate efficiently in vivo only when administered along with FeLV-A. Of six co-infected cats, three developed thymic lymphosarcomas, one severe aplastic anemia, and two cachexia and depression; all were viremic and seroconverted shortly after inoculation. While both virus types were detected in virtually all tissues examined from these tumor-bearing cats, there was a particularly noteworthy sequence reversion in the rFeLVs. It is known that exogenous FeLV isolates carry a conserved neutralizing MGPNL epitope in the middle of the surface glycoprotein domain of the env gene. In contrast, the parental recombinant viruses used to inoculate these cats harbored the enFeLV-derived MGPNP sequence at this position. However, all in vivo-propagated recombinants displayed the MGPNL sequence, while the env-encoded backbone flanking the MGPNL sequence was that of the parental recombinant virus. These results suggest that viruses with the MGPNL epitope have an in vivo proliferative advantage. The data also provide an explanation for the conservation of this epitope in exogenous FeLVs despite the existence of variant forms in enFeLV proviral elements with which they can recombine.
本研究旨在评估一组重组猫白血病病毒(rFeLVs)的体内感染性和致病性,这些重组病毒先前通过FeLV A亚群病毒(FeLV-A)与内源性FeLV(enFeLV)包膜(env)元件在体外进行强制重组而产生(Sheets等人,1992年,《病毒学》190卷,849 - 855页)。为了确定rFeLVs的感染性,给新生猫单独接种rFeLVs或与FeLV-A联合接种。重组病毒只有在与FeLV-A一起给药时才能在体内高效复制。在六只共同感染的猫中,三只发展为胸腺淋巴肉瘤,一只出现严重再生障碍性贫血,两只出现恶病质和抑郁;所有猫在接种后不久都出现病毒血症并发生血清转化。虽然在这些患肿瘤猫的几乎所有检测组织中都检测到了两种病毒类型,但rFeLVs中出现了一个特别值得注意的序列逆转。已知外源性FeLV分离株在env基因表面糖蛋白结构域中间携带一个保守的中和MGPNL表位。相比之下,用于接种这些猫的亲本重组病毒在该位置含有enFeLV衍生的MGPNP序列。然而,所有体内增殖的重组体都显示出MGPNL序列,而MGPNL序列两侧的env编码主干是亲本重组病毒的。这些结果表明,具有MGPNL表位的病毒在体内具有增殖优势。这些数据也解释了尽管enFeLV前病毒元件中存在可变形式且可与之重组,但外源性FeLVs中该表位仍具有保守性的原因。