How herpes viruses outsmart our immune system and survive for a lifetime in the body

Special mechanism protects herpesviruses from the immune system

After infection with herpesviruses, the viruses remain in the human body and can re-spread when weakened in the immune system. There are further health problems ranging from shingles to cancers. Scientists at the Helmholtz Center for Infection Research (HZI) have now deciphered how the carcinogenic Kaposi's sarcoma-associated herpesvirus (KSHV) protects against attacks by the immune system.

"The family of herpesviruses has adapted well to the immune system: their members manage to remain in the body of their host for life," explain the scientists. If the immune system of those affected weakened, but the viruses can multiply again and so "serious complications, including cancer, cause," report the researchers of the HZI. How the cancer-causing herpesviruses of the KSHV type manage to outsmart the immune system, the research team led by Prof. Melanie Brinkmann from Braunschweiger HZI could prove in a recent study. The researchers published their results in the journal "PLOS Pathogens".

Infections with herpesviruses are mainly known in the form of cold sores, but some herpesviruses can also cause cancer. (Image: Cherries / fotolia.com)

Every person becomes infected with herpesviruses over the course of their lives

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 the body of their host for a lifetime after infection. And "every person is infected with at least one of the nine representatives of human herpesviruses in the course of his life," reports the HZI. It succeeds in the immune system of healthy people in most cases to keep the virus in check, and rarely the development of severe disease symptoms.

Herpesviruses manipulate the body's immune system

According to the research team headed by Prof. Melanie Brinkmann, head of the working group "Viral Immunomodulation" at the Braunschweiger HZI and professor at the Hannover Medical School (MHH), herpesviruses manipulate their host's immune system "in a variety of ways" in order to remain in the host for life can. Weakening of the immune system threatens a renewed increase in herpesviruses, which could lead to serious complications, including cancers.

Carcinogenic herpesviruses

This applies, for example, in the Kaposi's sarcoma-associated herpesvirus - a tumor virus that can trigger three different cancers, explain the experts. The viruses are considered to trigger Kaposi's sarcoma (cancer of the blood vessels), the primary effusion lymphoma (white blood cell cancer) and Castleman's disease (lymph node disease). Kaposi's sarcoma is increasing in AIDS patients, "whose immune system is severely weakened by infection with the Human Immunodeficiency Virus 1 (HIV-1)," the researchers continue.

Protein ORF20 of particular importance

So far there is no vaccine against KSHV and also the mechanisms by which this virus manipulates its host and leads to the development of cancer, remain unclear, so the message of the HZI. The team led by Prof. Brinkmann has now studied a protein of this virus (the protein ORF20) that has been little characterized so far in order to better understand how KSHV elude immune control. "In order to treat infections with this herpes virus successfully, we need to understand in detail how it controls our immune system," emphasizes Prof. Melanie Brinkmann.

The nine members of the human herpesvirus family include Kaposi's sarcoma-associated herpesvirus (KSHV). Scientists at the HZI have now deciphered how the viruses outsmart the immune system. (Image: Spectral-Design / fotolia.com)

Herpes viruses use the immune system for their own purposes

By means of mass spectrometric analysis methods, the researchers were able to prove "that ORF20 forms a complex with a special host protein of the innate immune defense." The herpesviruses use virtually a component of the immune system for their own purposes. "Actually, this host protein, called OASL, serves as the host defense, so it has an antiviral function," explains the lead author of the study. Kendra Bussey in a press release of the HZI. However, 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 - thus it favors the infection process instead of stopping it."

Insights into the interaction between the virus and host

In their experiments with genetically modified viruses, the scientists were also able to determine that OASL is only proviral if the virus protein ORF20 is also present. This shows, according to Dr. Bussey, "that the KSHV can cleverly manipulate its host in his favor, beating him, so to speak, with his own means." In further studies, it now needs to be clarified which "lever of the cellular immune system" also uses the KSHV to outwit the immune system. "This will allow us to gain new insights into the interaction between the virus and its host and hopefully understand how this virus contributes to the development of cancer through the manipulation of the immune response," says Prof. Brinkmann. (Fp)