Ruby J, Bluethmann H, Peschon J J
Viral Engineering and Cytokines Group, Division of Immunology and Cell Biology, John Curtin School of Medical Research, Canberra 2601 Australia.
J Exp Med. 1997 Nov 3;186(9):1591-6. doi: 10.1084/jem.186.9.1591.
The antiviral nature of tumor necrosis factor (TNF) is generally well accepted. TNF appears to induce multiple antiviral mechanisms, and to synergize with interferon (IFN)-gamma in promoting antiviral activities. We infected TNF receptor (TNFR)-deficient mice with the virulent murine pathogen, ectromelia virus (EV), and observed that otherwise resistant mice were susceptible to lethal infection. To study the molecular basis of the antiviral action of TNF, mice were infected with a recombinant vaccinia virus encoding murine TNF (VV-HA-TNF). In normal mice, the replication of VV-HA-TNF was highly attenuated. In contrast, mice in which the TNFR type 1 (p55) or the TNFR type 2 (p75) were genetically disrupted showed a moderate defect in their capacity to clear the TNF-encoding virus. The contribution of both TNF receptors to the control of VV-HA-TNF was confirmed by the enhanced replication of VV-HA-TNF in mice deficient for both p55 and p75. These observations were corroborated by infecting TNFR-deficient mice with EV. For both infections, the p55 and p75 TNFRs were necessary to maintain normal levels of resistance. Thus, the antiviral activity of TNF is mediated via both TNFRs in vivo. Furthermore, these studies establish that TNF is an important component of the host response to a natural virus infection.
肿瘤坏死因子（TNF）的抗病毒特性已得到广泛认可。TNF似乎能诱导多种抗病毒机制，并在促进抗病毒活性方面与γ干扰素（IFN-γ）协同作用。我们用毒性很强的鼠病原体——鼠痘病毒（EV）感染了TNF受体（TNFR）缺陷型小鼠，发现原本具有抵抗力的小鼠变得易受致命感染。为了研究TNF抗病毒作用的分子基础，我们用编码鼠TNF的重组痘苗病毒（VV-HA-TNF）感染小鼠。在正常小鼠中，VV-HA-TNF的复制受到高度抑制。相比之下，1型TNFR（p55）或2型TNFR（p75）基因被破坏的小鼠在清除编码TNF的病毒的能力上存在中度缺陷。在p55和p75均缺陷的小鼠中，VV-HA-TNF的复制增强，这证实了两种TNF受体对控制VV-HA-TNF的作用。用EV感染TNFR缺陷型小鼠也证实了这些观察结果。对于这两种感染，p55和p75 TNFR都是维持正常抵抗力水平所必需的。因此，TNF的抗病毒活性在体内是通过两种TNFR介导的。此外，这些研究表明TNF是宿主对自然病毒感染反应的重要组成部分。
