Department of Bacteriology, School of Hygiene and Public Health, Johns Hopkins University, Baltimore.
J Exp Med. 1928 Sep 30;48(4):475-92. doi: 10.1084/jem.48.4.475.
Fifty-eight white and hooded rats have been splenectomized and all of them have shown a more or less severe anemia and an infection of the red blood cells with Bartonella muris. Another strain of white rats obtained from Littlestown showed no anemia and no bartonellas in the blood after splenectomy, until exposed to infected rats. Others of these Littlestown rats, kept in the laboratory for some time before operation and exposed to infected rats, came down with bartonella anemia within 6 days after splenectomy. Whole blood or the washed red blood corpuscles from splenectomized rats which show bartonellas and anemia will produce a similar condition in young rats when injected intraperitoneally. Adult rats of strains which harbor the virus (as demonstrated by splenectomy) cannot be infected by injection. Intravenous inoculation of young normal rabbits with blood from an infected rat will sometimes produce a similar infection and anemia in the rabbit, and the virus can then be transferred back to young rats. The virus of rat anemia may be transferred from young normal rat to young normal rat with the appearance of Bartonella muris and the production of anemia. In the early transfers the disease may be fatal, but it usually becomes milder in successive passages. Although we have not yet been able to cultivate Bartonella muris and prove its etiological relationship to rat anemia by inoculation of cultures, we have added to the evidence that Bartonella muris is the cause of the anemia. Washed red blood corpuscles, containing bartonellas, will produce the anemia in the usual way while plasma from the same cells will either fail to produce it altogether or only after a prolonged incubation period. Blood heated to 57 degrees C. for (1/2) hour fails to produce anemia or the appearance of bartonellas in the blood of inoculated animals. From these observations the following conclusions may be drawn: 1. All rats which harbor Bartonella muris ratti come down with a more or less severe anemia after splenectomy. 2. Young rats which have not yet developed an immunity undergo the typical anemia after intraperitoneal injection of blood from a splenectomized animal in the early stages of the anemia. 3. Young rabbits may show bartonellas and develop anemia following intravenous inoculation of infected blood. 4. The virus of rat anemia and Bartonella muris ratti may be transferred from normal animal to normal animal for successive generations. Such strains have now been transferred for five, nine and thirty generations. 5. The resistance of rats to bartonella anemia is almost wholly dependent on the spleen. Other organs do not take over this function of protection as shown by the relapse of splenectomized rats many months after recovery. Young rats which have recovered from an attack of anemia are not protected by this previous infection from the invasion of the virus following splenectomy. Adult splenic tissue mixed with infected blood before injection does not inhibit or neutralize the virus. 6. The virus of rat anemia is highly contagious and rats exposed to infection acquire it in some unknown way. 7. Bartonella muris ratti represents the virus of rat anemia or at least cannot be separated from the virus because: (a) The anemia in splenectomized and injected animals is always preceded by the appearance of bartonellas and the grade of anemia is proportional to the degree of infection with bartonellas. (b) Washed corpuscles containing bartonellas always produce anemia. Plasma either fails to do so, or produces a mild anemia after a long incubation period with a few bartonellas in the blood. (c) The thermal death point of virus and bartonella is the same.
58 只白色和带帽的老鼠进行了脾切除术,所有这些老鼠都表现出不同程度的贫血和红细胞感染巴尔通体鼠。从小镇获得的另一批白色老鼠在脾切除术后没有贫血,也没有血液中的巴尔通体,直到接触感染的老鼠。这些来自利特尔斯敦的老鼠中的一些,在手术前在实验室中饲养了一段时间,并接触了感染的老鼠,在脾切除后 6 天内出现了巴尔通体贫血。来自脾切除后显示巴尔通体和贫血的老鼠的全血或洗涤的红细胞,当注射到腹腔内时,会在幼鼠中引起类似的情况。携带病毒的成年大鼠(如脾切除术所示)不能通过注射感染。将来自感染大鼠的血液静脉内接种给年轻正常兔,有时会在兔子中引起类似的感染和贫血,并且可以将病毒转回给年轻大鼠。鼠贫血病毒可能从年轻正常大鼠转移到年轻正常大鼠,出现巴尔通体鼠和贫血。在早期转移中,疾病可能是致命的,但在连续传代中通常会变得更温和。尽管我们尚未能够培养巴尔通体鼠,并通过接种培养物来证明其与鼠贫血的病因关系,但我们增加了证据表明巴尔通体鼠是贫血的原因。含有巴尔通体的洗涤红细胞通常以这种方式产生贫血,而来自相同细胞的血浆则根本不会产生贫血,或者仅在长时间孵育后才会产生贫血。在 57 摄氏度下加热 1/2 小时的血液不能在接种动物的血液中产生贫血或巴尔通体的出现。从这些观察结果可以得出以下结论:
所有携带巴尔通体鼠的大鼠在脾切除术后都会出现不同程度的贫血。
在贫血的早期阶段,尚未产生免疫力的幼鼠通过腹腔内注射来自脾切除动物的血液,会经历典型的贫血。
静脉内接种感染血液后,年轻兔子可能会出现巴尔通体并发生贫血。
鼠贫血病毒和巴尔通体鼠可以从正常动物转移到正常动物,连续传代。这样的品系现在已经传代了五代、九代和三十代。
大鼠对巴尔通体贫血的抵抗力几乎完全依赖于脾脏。其他器官不能接管这种保护功能,脾切除后的大鼠在恢复后数月内会复发。从贫血发作中恢复的年轻大鼠不会因脾切除后的先前感染而受到该病毒的侵袭的保护。注射前与感染血液混合的成年脾组织不能抑制或中和病毒。
鼠贫血病毒具有高度传染性,接触感染的大鼠会以某种未知的方式获得它。
巴尔通体鼠代表了鼠贫血病毒,或者至少不能与病毒分离,因为:(a)脾切除和注射动物中的贫血总是先于巴尔通体的出现,贫血的程度与巴尔通体的感染程度成正比。(b)含有巴尔通体的洗涤红细胞总是会引起贫血。血浆要么根本不会引起贫血,要么在血液中含有少量巴尔通体后经过长时间孵育才会引起轻度贫血。(c)病毒和巴尔通体的热死亡点相同。