Hepatitis C Uses Decoys to Survive Immune System Attacks

Researchers find cooperation among viral variants that help hepatitis C to survive.

The hepatitis C virus (HCV) employs methods commonly used during war to fool the enemy, a recent study suggests.

Following infection with HCV, the virus evolves multiple variants, including a group of viral particles that act as decoys to protect the other particles from attack by the immune system so they can launch a different attack. The study, published recently in the journal Proceedings of the National Academy of Sciences, utilized a mathematical model to analyze interaction between viral variants and immune system antibodies in a group of HCV patients, some of whom were tracked for up to 20 years.

"The members of viral populations in Hepatitis C don't act like separate entities; the different variants work together almost like a team," said researcher Leonid Bunimovich, of the Georgia Tech School of Mathematics, in a press release. "There is a clear separation of responsibilities, including variants we call 'altruistic' because they sacrifice themselves for the good of the whole viral population. These variants seem to draw the immune system attack on themselves."

HCV was found to evolve differently in each person to generate a mixture of genetically-related variants, which comprise a complex network in which the virus mutates to survive attacks from the immune system.

"The virus variants do not communicate directly with one another, but in this system of viruses and antibodies, they interact through the antibodies," Bunimovich said. "When one antibody-producing cell responds to one variant, and then to another, that is a form of interaction that affects both variants. An indirect interaction occurs when the virus variants interact with the same antibody in the network."

Through next-generation gene sequencing, the researchers examined the genetic compositions of viral populations, and even saw evolution in blood samples taken from the same persons over time. Variant populations were found to fluctuate, with some in small numbers and others reappearing after seemingly being eradicated by the immune system.

The results showed that certain variants provoked a response by the immune system to protect other variants, as part of a process called antigenic cooperation. The findings may lead future treatments to account for how the virus evolves differently in each patient.

"The altruistic variants allow the antibodies to attack them, thereby sacrificing themselves, so other variants can survive," said first author Pavel Skums. "The altruistic variants fool the immune system, rendering the immune system response to other variants ineffective. In essence, the surviving variants use the altruistic variants as an umbrella to protect themselves."