The therapeutic effects of melatonin against viral infections, with emphasis on the Venezuelan equine encephalomyelitis (VEE), are reviewed. Melatonin has been shown to prevent paralysis and death in mice infected with the encephalomyocarditis virus and to decrease viremia. Melatonin also postpones the onset of the disease produced by Semliki Forest virus inoculation and reduces the mortality of West Nile virus-infected mice stressed by either isolation or dexamethasone injection. An increase in the host resistance to the virus via a peripheral immunostimulatory activity is considered responsible for these effects. It has also been demonstrated that melatonin protects some strains of mink against Aleutian disease, and prevents the reduction of B- and T-cells as well as Th1 cytokine secretion in mice infected with leukemia retrovirus. In VEE-infected mice, melatonin postpones the onset of the disease and death for several days and reduces the mortality rate. This protective effect seems to be due to the increase in the production of interleukin-1beta (IL-1beta), as 100% of the infected mice treated with melatonin die when IL-1beta is blocked with antimurine IL-1beta antibodies. Although melatonin administration raises serum levels of tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma), the mortality observed in neutralization experiments with the corresponding anticytokine antibodies, suggests that neither TNF-alpha nor IFN-gamma are essential for the protective effect of melatonin on murine VEE virus infection. Melatonin treatment also enhances the efficiency of immunization against the VEE virus. Reactive oxygen species have been implicated in the dissemination of this virus, and their deleterious effects may be diminished by melatonin. This indole inhibits nitric oxide synthetase activity and it is a potent scavenger of nitric oxide, which also plays an important role in the spread of the VEE virus. In conclusion, the immunomodulatory, antioxidant, and neuroprotective effects of melatonin suggest that this indole must be considered as an additional therapeutic alternative to fight viral diseases.

中文翻译：

---

褪黑激素和病毒感染。

综述了褪黑激素对病毒感染的治疗作用，重点是委内瑞拉马脑脊髓炎（VEE）。褪黑素已被证明可预防感染了脑心肌炎病毒的小鼠的瘫痪和死亡，并降低病毒血症。褪黑激素还可以延缓Semliki Forest病毒接种所致疾病的发作，并降低隔离或注射地塞米松对西尼罗河病毒感染小鼠的死亡率。宿主通过外围免疫刺激活性对病毒的抗性增加被认为是造成这些影响的原因。还已经证明，褪黑素可以保护一些貂皮免受阿留申氏病的侵害，并可以防止白血病逆转录病毒感染的小鼠体内B细胞和T细胞的减少以及Th1细胞因子的分泌。在被VEE感染的小鼠中，褪黑素将疾病的发作和死亡推迟了几天，并降低了死亡率。这种保护作用似乎是由于白介素-1β（IL-1beta）的产生增加所致，因为当用抗鼠IL-1beta抗体阻断IL-1beta时，用褪黑素治疗的100％受感染小鼠死亡。尽管褪黑激素给药可提高血清肿瘤坏死因子-α（TNF-α）和干扰素-γ（IFN-γ）的血清水平，但在用相应的抗细胞因子抗体进行中和实验中观察到的死亡率表明，TNF-α和IFN-γ都不是褪黑素对鼠VEE病毒感染的保护作用至关重要。褪黑素治疗还提高了针对VEE病毒的免疫效率。活性氧已与这种病毒的传播有关，褪黑激素可能会降低其有害作用。该吲哚抑制一氧化氮合成酶的活性，并且是一氧化氮的有效清除剂，在VEE病毒的传播中也起着重要作用。总之，褪黑激素的免疫调节，抗氧化剂和神经保护作用表明，该吲哚必须被视为对抗病毒性疾病的另一种治疗替代方法。