A special mechanism protects herpes viruses from the immune system
After an infection with herpes viruses, the viruses remain in the human body and can spread again if the immune system is weakened. There are other health problems that range from shingles to cancer. Scientists at the Helmholtz Center for Infection Research (HZI) have now deciphered how the cancer-causing Kaposi sarcoma-associated herpes virus (KSHV) protects itself against attacks by the immune system.
"The family of herpes viruses has adapted extremely well to the immune system: Its members manage to remain in their host's body for life after the infection," the scientists explain. If the affected person's immune system is weakened, however, the viruses can multiply again, causing “serious complications, including cancer,” report the HZI researchers. The research team led by Prof. Melanie Brinkmann from the Braunschweig HZI was able to demonstrate in a recent study how the cancer-causing herpes viruses of the KSHV type succeed in outwitting the immune system. The researchers published their results in the specialist journal “PLOS Pathogens”.
Every person becomes infected with herpes viruses during their life
In most infectious diseases, the pathogens are completely eliminated by the immune system in the course of healing, but herpes viruses manage to remain in their host's body for life after the infection. And "every person is infected with at least one of the nine representatives of the human herpes virus in the course of their life," reports the HZI. In most cases, the immune system of healthy people manages to keep the virus in check, and the development of severe symptoms of the disease is rarely noticed.
Herpes viruses manipulate the body's immune system
According to the research team led by Prof. Melanie Brinkmann, head of the "Viral Immunomodulation" working group at the Braunschweig HZI and professor at the Hannover Medical School (MHH), herpes viruses manipulate their host's immune system "in a variety of ways" in order to remain in the host for life can. If the immune system is weakened, the herpes viruses may multiply again, which could result in serious complications and even cancer.
Carcinogenic herpes viruses
This applies, for example, to the Kaposi sarcoma-associated herpes virus - a tumor virus that can trigger three different types of cancer, the experts explain. The viruses are thought to trigger Kaposi's sarcoma (cancer of the blood vessels), primary effusion lymphoma (cancer of the white blood cells) and Castlemann’s disease (disease of the lymph nodes). Kaposi's sarcoma increasingly occurs in AIDS patients whose immune system is severely weakened by infection with the Human Immunodeficiency Virus 1 (HIV-1), the researchers continue to report.
Protein ORF20 with special meaning
So far there is no vaccine against KSHV and the mechanisms by which this virus manipulates its host and leads to the development of cancer remain unclear, according to the HZI. The team led by Prof. Brinkmann has now investigated a previously poorly characterized protein of this virus (the protein ORF20) in order to better understand how KSHV evades immune control. "In order to successfully treat infections with this herpes virus, we have to understand in detail how it controls our immune system," emphasizes Prof. Melanie Brinkmann.
Herpes viruses use the immune system for their own purposes
Using mass spectrometric analysis methods, the researchers were able to demonstrate “that ORF20 forms a complex with a special host protein of the innate immune system.” The herpes viruses practically use a component of the immune system for their own purposes. "This host protein, called OASL, actually serves to defend the host, so it has an antiviral function," explains the first author of the study, Dr. Kendra Bussey in a press release from the HZI. Now, according to their own statements, the researchers were able "to show for the first time that OASL has a proviral function in the context of KSHV infection - it therefore favors the course of the infection instead of stopping it."
Insights into the interaction between the virus and the host
In their experiments with genetically modified viruses, the scientists were also able to determine that OASL only has a proviral effect if the virus protein ORF20 is also present. According to Dr. Bussey, "that the KSHV can manipulate its host skilfully in its favor, that it beats it with its own resources, so to speak." In further studies, it is now necessary to clarify which "lever of cellular immune defense" the KSHV also uses to outwit the immune system. "This will give us new insights into the interaction between the virus and its host and hopefully will enable us to understand how this virus contributes to the development of cancer by manipulating the immune response," said Prof. Brinkmann. (fp)