Raslova H, Mistrikova J, Kudelova M, Mishal Z, Sarasin A, Blangy D, Berebbi M
Institute of Virology, Slovak Academy of Sciences, Bratislava.
Viral Immunol. 2000;13(3):313-27. doi: 10.1089/08828240050144644.
Inbred athymic nude mice (BALB/c) were injected subcutaneously with the wild-type murine gammaherpesvirus 72 (MHV-72), which has been shown to induce the infectious mononucleosis (IM)-like syndrome in immunocompetent mice. The mice were also injected with UV-irradiated MHV-72. We studied the pattern of acute and chronic infection in the blood cells of the nude mice and detected viral DNA sequences in the infected leukocytes by polymerase chain reaction (PCR) technique up to when the animal died, close to 1 month postinfection. Using the UV-irradiated virus that induces an increase in mouse survival time, the viral sequences were present in the blood up to 3 months postinfection, then disappeared. We detected atypical lymphocytes in the blood of mice infected with both wt and UV-irradiated viruses. These atypical cells were similar in shape to those present in the blood of patients with IM induced by Epstein-Barr virus (EBV). Via Unscheduled DNA Synthesis (UDS), DNA synthesis was demonstrated in the atypical cells whose phenotype is identical to that of B cells, as shown with a panel of monoclonal antibodies. By double immunofluorescence staining, using an hyperimmune anti-MHV-72 serum and an anti-IgG + IgM + IgA monoclonal antibody, we demonstrated that these atypical B cells express some viral antigens. Contrary to the immunocompetent mice, the nude mice did not develop splenomegaly after infection with wt virus, probably due to the lack of T cell subsets. However, we observed an increase of nude mice B cells in the spleen. The nude mice died 1 month postinfection showing a high frequency (40%) of atypical lymphoblast-like B-cells in the blood; the increase in natural killer (NK) cell number was not detected after infection. Such findings suggest that NK cells probably did not play an important role in immune response to the MHV infection in nude mice. Finally, this mouse model could play an important role in antigammaherpesviral therapy of immunocompromised patients.
将近交系无胸腺裸鼠（BALB/c）皮下注射野生型鼠γ疱疹病毒72（MHV - 72），该病毒已被证明能在免疫活性小鼠中诱发传染性单核细胞增多症（IM）样综合征。这些小鼠还被注射了紫外线照射的MHV - 72。我们研究了裸鼠血细胞中的急性和慢性感染模式，并通过聚合酶链反应（PCR）技术在感染的白细胞中检测病毒DNA序列，直至动物死亡，即感染后近1个月。使用能延长小鼠存活时间的紫外线照射病毒，病毒序列在感染后3个月内存在于血液中，然后消失。我们在感染野生型和紫外线照射病毒的小鼠血液中均检测到非典型淋巴细胞。这些非典型细胞的形态与由爱泼斯坦 - 巴尔病毒（EBV）诱发的IM患者血液中的细胞相似。通过非预定DNA合成（UDS），在表型与B细胞相同的非典型细胞中证明了DNA合成，这通过一组单克隆抗体得以显示。通过双重免疫荧光染色，使用超免疫抗MHV - 72血清和抗IgG + IgM + IgA单克隆抗体，我们证明这些非典型B细胞表达一些病毒抗原。与免疫活性小鼠相反，裸鼠感染野生型病毒后未出现脾肿大，这可能是由于缺乏T细胞亚群。然而，我们观察到裸鼠脾脏中的B细胞有所增加。裸鼠在感染后1个月死亡，血液中出现高频（40%）的非典型淋巴母细胞样B细胞；感染后未检测到自然杀伤（NK）细胞数量增加。这些发现表明NK细胞可能在裸鼠对MHV感染的免疫反应中未发挥重要作用。最后，这种小鼠模型可能在免疫受损患者的抗γ疱疹病毒治疗中发挥重要作用。
