Crawford T B, Wardrop K J, Tornquist S J, Reilich E, Meyers K M, McGuire T C
Department of Veterinary Microbiology, Washington State University, Pullman 99164-7040, USA.
J Virol. 1996 Nov;70(11):7842-50. doi: 10.1128/JVI.70.11.7842-7850.1996.
The purpose of this study was to identify the mechanisms responsible for the thrombocytopenia that develops following infection of horses by the lentivirus equine infectious anemia virus (EIAV). Immunocompetent Arabian foals and Arabian foals with severe combined immunodeficiency (SCID), which lack functional B and T lymphocytes, were experimentally infected with EIAV. Levels of viremia and a number of clinical and hematologic parameters were examined prior to and following infection. Thrombocytopenia was not dependent on the immune response: SCID foals were affected as severely as immunocompetent foals. Production of platelets, measured by metabolic incorporation of radioactive label, was significantly reduced. The decrease ranged from 35 to 89% in three SCID and two immunocompetent foals examined. Platelet survival, measured by 51Cr labeling, also declined following infection in both SCID and immunocompetent foals: 51 and 68%, respectively, relative to the preinfection life spans. The difference between immunocompetent and immunodeficient foals was not statistically significant. The number of megakaryocytes (MK) per square millimeter of bone marrow, determined by digitizing morphometry, was not significantly altered in either SCID or immunocompetent thrombocytopenic foals. Numbers of denuded MK nuclei per unit area increased, but the elevation was not statistically significant. No evidence for viral replication in MK was found. Three different parameters of intravascular coagulation (activated prothombin time, fibrin degradation products, and one-step prothombin time) remained normal until after platelet numbers had declined significantly, arguing against an important role for disseminated intravascular coagulation. The findings indicate that EIAV induces thrombocytopenia principally through an indirect, noncytocidal suppressive effect on platelet production, the mechanism of which is unknown. A shortening of platelet life span apparently contributes moderately to the platelet deficit as well. The shortening of platelet life span is multifactorial in origin, including both mechanisms that depend on an active immune response and those that do not.
本研究的目的是确定慢病毒马传染性贫血病毒（EIAV）感染马匹后发生血小板减少症的机制。将具有免疫能力的阿拉伯驹和缺乏功能性B和T淋巴细胞的严重联合免疫缺陷（SCID）阿拉伯驹用EIAV进行实验性感染。在感染前后检查病毒血症水平以及一些临床和血液学参数。血小板减少症不依赖于免疫反应：SCID驹与具有免疫能力的驹受到的影响一样严重。通过放射性标记的代谢掺入来测量的血小板生成显著减少。在检查的3匹SCID驹和2匹具有免疫能力的驹中，减少幅度在35%至89%之间。通过51Cr标记测量的血小板存活时间在SCID驹和具有免疫能力的驹感染后也均下降：相对于感染前的寿命，分别下降了51%和68%。具有免疫能力的驹和免疫缺陷的驹之间的差异无统计学意义。通过数字化形态测量法确定的每平方毫米骨髓中巨核细胞（MK）的数量在SCID或具有免疫能力的血小板减少驹中均无显著改变。单位面积裸露的MK核数量增加，但升高无统计学意义。未发现MK中有病毒复制的证据。直到血小板数量显著下降后，血管内凝血的三个不同参数（活化凝血酶原时间、纤维蛋白降解产物和一步凝血酶原时间）仍保持正常，这表明弥散性血管内凝血不起重要作用。研究结果表明，EIAV主要通过对血小板生成产生间接的、非杀细胞性的抑制作用来诱导血小板减少症，其机制尚不清楚。血小板寿命缩短显然也对血小板缺乏有一定程度的影响。血小板寿命缩短的原因是多方面的，包括依赖于活跃免疫反应的机制和不依赖于活跃免疫反应的机制。
