科学家在病毒引发的癌症研究领域取得突破性成就

  发表于国际杂志Cell Host and Microbe上的一篇研究论文中，来自佛罗里达州立大学的研究人员表示他们在抵御癌症领域研究取得了重大突破，这或为开发癌症新型疗法提供新的希望。研究者Fanxiu Zhu说道，我们发现细胞中一种特殊病毒蛋白KicGas或可抑制机体主要的DNA感受器，从而可使得机体对病毒感染产生反应，这就说明，对这种细胞通路进行操控或可帮助个体抵御感染、癌症或自身免疫疾病。
  通过对KicGas及其感受器进行操控或许就可以增强或下调机体免疫反应来帮助抵御机体感染以及自身免疫疾病的发生；研究者目前正在研究揭示DNA病毒如何引发癌症，大约15%的人类癌症病例都是由病毒引起的，因此科学家们尝试通过多种途径来寻找答案，帮助解释机体如何应对病毒感染以及某些病毒如何在机体维持长期的感染。
  此前研究中研究人员在细胞中鉴别出了名为cGas的主要DNA感受器，基于此研究人员就在人类疾病的背景下对这种DNA感受器进行了深入的研究，因为从理论上来讲感受器可以向机体发送警惕信号来抵御DNA病毒引发的机体感染。从本质上来讲DNA病毒就是一种包含遗传物质的胞内寄生物，很多疾病比如天花、疱疹以及水痘都是由DNA病毒所引起的，这些疾病之所以非常难以治疗的其中一个原因就是病毒会利用宿主机体细胞的细胞器来为自己服务。
  文章中研究者对一种人类疱疹病毒—Kaposi肉瘤相关疱疹病毒(KSHV)进行研究，这种病毒会引发淋巴瘤和卡波西肉瘤，这两种癌症是AIDS患者及其它免疫缺陷个体常患的癌症。研究者对总计90个KSHV细胞中的每一个蛋白进行筛查，最终发现其中有一种特殊蛋白对细胞内的DNA传感器cGas起到了抑制作用，随后研究者利用卡波西肉瘤感染人类细胞系来模拟自然的感染状态，结果发现当消除抑制蛋白KicGas后，细胞就会产生强效的免疫反应。
  研究者Hong Li表示，我们主要在测试管中研究特殊蛋白抑制cGas活性的分子机制，下一步我们还将建立相互作用的三维模型来帮助理解这种抑制作用发生的原因，相信通过后期更为深入的研究可以帮助我们设计出更多新型疗法来治疗人类疾病。（转化医学网360zhyx.com）
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Scientists identify possible key in virus, cancer research

Florida State University researchers have taken a big step forward in the fight against cancer with a discovery that could open up the door for new research and treatment options. 

Fanxiu Zhu, the FSU Margaret and Mary Pfeiffer Endowed Professor for Cancer Research, and his team uncovered a viral protein in the cell that inhibits the major DNA sensor and thus the body's response to viral infection, suggesting that this cellular pathway could be manipulated to help a person fight infection, cancer or autoimmune diseases.

They named the protein KicGas.

"We can manipulate the protein and/or the sensor to boost or tune down the immune response in order to fight infectious and autoimmune diseases, as well as cancers," Zhu said.

The study was published today in the journal Cell Host and Microbe.

Zhu leads a research team investigating how DNA viruses can cause cancer, a major focus of researchers worldwide. About 15 percent of human cancer cases are caused by viruses, so scientists have been seeking answers about how the body responds to viral infection and how some viruses maintain life-long infections.

In the past few years, researchers finally identified the major DNA sensor in cells, known as cGas. That spurred researchers to further examine this sensor in the context of human disease because ideally that sensor should have been alerting the body to fight disease brought by a DNA virus.

Essentially, a DNA virus is an intracellular parasite that contains genetic material. Several notable diseases including smallpox, herpes, and chickenpox are caused by DNA viruses. One of the reasons these diseases are so difficult to cure is because they take over the cellular machinery of their human host, often making it impossible to kill the virus without also harming the person.

Although people are equipped with sophisticated immune systems to cope with viral infection, many viruses have co-evolved mechanisms to evade or suppress the body's immune responses.

So the discovery of this protein is critical to further exploration of how these DNA viruses work and how they can be thwarted.

To uncover this protein, Zhu's team studies Kaposi's sarcoma-associated herpesvirus (KSHV), a human herpesvirus that causes some forms of lymphoma and Kaposi's sarcoma, a cancer commonly occurring in AIDS patients and other immunocompromised individuals.

In this study, researchers screened every protein in a KSHV cell—90 in total—and ultimately found that one of them directly inhibited the DNA sensor called cGAS. They infected human cell lines with the Kaposi's sarcoma virus to mimic natural infection, and found when they eliminated the inhibitor protein—KicGas—the cells produced a much stronger immune response......