耶鲁大学：当你的体温降低时，身体的防御机制失灵 病毒入侵扩散

Yale University:Cold Viruses Attack When Your Immune System Is Cold

去年，由耶鲁大学的Ellen Foxman和Akiko Iwasaki领导的一个研究小组为一个流行的观点提供了有力的证据，那就是在寒冷的天气里一个人更容易感冒。他们发现，当小鼠在低于正常体温的温度下孵育时，它们的细胞对引起普通感冒的鼻病毒反应迟钝。

特别是,老鼠细胞分泌更少的干扰素，对干扰素的应答也降低。干扰素是一种抗病毒防御分子。因此，他们的研究证明了一种合理的分子机制来解释这种现象。

现在，研究人员带回了更多的证据。这一次,他们检查人体细胞和聚焦于与干扰素-β无关的免疫过程。

故意自杀即细胞凋亡是细胞处理病毒感染的一种方式。虽然这个过程会导致细胞死亡，但它有助于防止病毒扩散到其他细胞。但是，在一组实验中，研究小组发现，如果将受感染的细胞放在摄氏33度，比正常体温低4度的环境中，它们自杀的可能性要小得多。(见图)。

图1：病毒感染引起的细胞凋亡在摄氏33度时减慢。

图的左侧描述了使用未感染细胞的控制条件。(“模拟”感染是该行业使用的术语。)然后对细胞进行染色，观察是否存在双链RNA (dsRNA，表示病毒感染)和蛋白casp3 (casp3+，表示细胞凋亡已被激活)。如左图所示，染色模式显示细胞既没有被感染也没有发生凋亡。这是意料之中的，因为这些框表示控制条件。
图的右边描绘了细胞被鼻病毒感染的实验条件。请注意，虽然两个盒子都显示出dsRNA的存在，表明病毒感染，但只有一小部分细胞在33度时凋亡，而不是37度。(见红色圈出的百分比)结果很明显:更低的温度降低了受感染细胞的自杀能力。

控制病毒感染的分子机制。控制病毒感染的分子机制。
进一步的实验表明，当研究人员抑制细胞凋亡和RNaseL(一种破坏dsRNA的细胞酶)时，鼻病毒甚至在生长在37度c的细胞内增殖。
利用他们的数据，作者构建了一个模型，他们相信在一个受感染细胞内发生了什么。dsRNA的检测向细胞发出病毒存在的警报。然后细胞激活凋亡和RNaseL。在正常情况下，这可能有助于防止病毒的传播。但是在较低的温度下(比如在我们的呼吸道中发现的那些)，这些机制不能很好地工作，使我们容易感染鼻病毒。

所以，当冬天来临的时候，一定要在你的鼻子和嘴巴上戴一条围巾……不情愿地承认妈妈是对的。

　

Cold Viruses Attack When Your Immune System Is Cold

 Last year, a team of researchers led by Ellen Foxman and Akiko Iwasaki of Yale University provided supporting evidence for the popular notion that being in cold weather makes a person more susceptible to catching cold. They showed that mouse cells do not respond well to rhinovirus, a cause of the common cold, when incubated at temperatures lower than normal body temperature.

In particular, mouse cells secreted less and were less responsive to interferon-β, a type of antiviral defense molecule. Thus, their research demonstrated a plausible molecular mechanism to explain the phenomenon. Now, the researchers are back with yet more evidence. This time, they examined human cells and focused on immune processes that were not related to interferon-β. Intentional suicide (i.e., apoptosis) is one way that cells handle viral infection. Though this process results in the death of the cell, it helps prevent the spread of the virus to other cells. But, in one set of experiments, the team showed that infected cells were much less likely to commit suicide if they were incubated at 33 degrees C., which is four degrees lower than normal body temperature. (See figure.) Apoptosis triggered by viral infection is slowed at 33 degrees C.Apoptosis triggered by viral infection is slowed at 33 degrees C. The left-hand side of the figure depicts the control condition using cells that were not infected. ("Mock" infection is the term used in the trade.) Cells were then stained for the presence of double-stranded RNA (dsRNA, which indicates viral infection) and the protein caspase-3 (casp3+, which indicates that apoptosis has been activated). As depicted in both left-hand boxes, the staining patterns showed that cells were neither infected nor undergoing apoptosis. That is to be expected, since these boxes represent control conditions. The right-hand side of the figure portrays the experimental conditions in which cells were infected by rhinovirus. Notice that while both boxes show the presence of dsRNA, indicating viral infection, only a fraction of cells are undergoing apoptosis at 33 degrees compared to 37 degrees. (See the percentages circled in red.) The result is clear: A colder temperature slows down an infected cell's ability to commit suicide. A molecular mechanism that keeps viral infections in check.A molecular mechanism that keeps viral infections in check. Further experiments showed that when researchers suppressed apoptosis and RNaseL, a cellular enzyme that destroys dsRNA, rhinovirus proliferated even inside cells that were grown at 37 degrees C. This conclusively demonstrated the importance of these mechanisms for keeping viral infections in check. With their data, the authors constructed a model of what they believe is occurring inside an infected cell. Detection of dsRNA alerts the cell to the presence of a virus. The cell then activates apoptosis and RNaseL. In normal conditions, this may help prevent the spread of the virus. But at cooler temperatures (such as those found in our airways), these mechanisms don't work very well, leaving us susceptible to rhinovirus infection. So, when winter comes, be sure to wear a scarf around your nose and mouth... and begrudgingly admit that mom was right. Update (5:21 pm PT, July 11, 2016) Dr. Iwasaki kindly provided a figure that beautifully summarizes his team's model. Courtesy of Dr. Akiko Iwasaki.Courtesy of Dr. Akiko Iwasaki. ### Source: Ellen F. Foxman, James A. Storer, Kiran Vanaja, Andre Levchenko, and Akiko Iwasaki. "Two interferon-independent double-stranded RNA- induced host defense strategies suppress the common cold virus at warm temperature." PNAS. Published online: 11-July-2016. DOI: 10.1073/pnas.1601942113 Cold Viruses Attack When Your Immune System Is Cold | American Council on Science and Health https://www.acsh.org/news/2016/07/11/cold-viruses-attack-when-your-immune-system-is-cold