THE LEUKEMOGENIC POTENTIAL OF AN ENHANCER VARIANT OF MOLONEY MURINE LEUKEMIA-VIRUS VARIES WITH THE ROUTE OF INOCULATION

THE LEUKEMOGENIC POTENTIAL OF AN ENHANCER VARIANT OF MOLONEY MURINE LEUKEMIA-VIRUS VARIES WITH THE ROUTE OF INOCULATION
复制标题

DOI:
10.1128/jvi.68.11.6883-6889.1994
复制
发表时间:
1994-11-01
影响因子:
5.4
通讯作者:
FAN, H
FAN, H
中科院分区:
医学2区
文献类型:
--
作者:
BELLI, B;FAN, H

文献摘要

被引文献

相似文献

我们先前表明,莫洛尼鼠白血病病毒(M-MuLV)的Mo+ PyF 101变体在皮下(s.c.)植入新生小鼠体内我们最近发现腹膜内(i. p.)用相同病毒接种新生小鼠显著增强其致白血病性。本研究比较了两种不同接种途径对新生小鼠的感染情况。我们研究了病毒在体内的复制,以确定关键的白血病前事件。这些在腹膜内接种Mo+ PyF 101 M-MuLV的小鼠中观察到,但在皮下接种时未观察到。感染中心试验表明,与野生型M-MuLV相比,无论接种途径如何,Mo+ PyF 101 M-MuLV均显示胸腺感染延迟。另一方面,IP-接种的小鼠比s.c.-接种动物。因此,腹膜内接种的致白血病性增强与骨髓的有效早期感染相关,而与胸腺的早期感染无关。这些结果表明骨髓感染在Mo+ PyF 101 M-MuLV感染小鼠中有效白血病发生中的作用。与这一观点一致,如果通过腹膜内注射10至12日龄动物减少骨髓感染,白血病发生类似于s.c.接种。因此,涉及两种对诱导有效白血病至关重要的细胞类型。一个细胞从s.c.部位递送病毒。接种(皮肤)至骨髓,并且明显限制Mo+ PyF 101 M-MuLV复制。第二细胞位于骨髓中,其早期感染是有效的白血病发生所必需的。
We previously showed that the Mo+PyF101 variant of Moloney murine leukemia virus (M-MuLV) is poorly leukemogenic when inoculated subcutaneously (s.c.) into neonatal mice. We recently found that intraperitoneal (i.p.) inoculation of neonatal mice with the same virus significantly enhanced its leukemogenicity. In this study, infections of neonatal mice by the two different routes of inoculation were compared. We studied replication of the virus in vivo to identify critical preleukemic events. These would be observed in mice inoculated i.p. by Mo+PyF101 M-MuLV but not when inoculation was s.c. Infectious center assays indicated that regardless of the route of inoculation, Mo+PyF101 M-MuLV showed delayed infection of the thymus compared with wild-type M-MuLV. On the other hand, i.p.-inoculated mice showed more rapid appearance of infectious centers in the bone marrow than did s.c.-inoculated animals. Thus, the enhanced leukemogenicity of i.p. inoculation correlated with efficient early infection of the bone marrow and not,with early infection of the thymus. These results suggest a role for bone marrow infection for efficient leukemogenesis in Mo+PyF101 M-MuLV-infected mice. Consistent with this notion, if bone marrow infection was decreased by injecting 10- to 12-day old animals i.p., leukemogenicity resembled that of s.c. inoculation. Thus, two cell types that are critical for the induction of efficient leukemia were implicated. One cell delivers virus from the site of s.c. inoculation (the skin) to the bone marrow and is apparently restricted for Mo+PyF101 M-MuLV replication. The second cell is in the bone marrow, and its early infection is required for efficient leukemogenesis.