A team of scientists discovered a new method used by skin papillomaviruses to trick the immune system. The viruses could generate a bait to attract antibodies.
The sly move of cutaneous papillomaviruses was unveiled by scientists at the German Cancer Research Center (DKFZ), a national cancer research center in Germany. The viruses could release a fake protein for antibodies to bind to. This would prevent the neutralization of the pathogens. If the viruses prevailed, they could infect skin cells, alter their DNA, and induce cellular malignancy. Moreover, the immune system could take months to detect the ruse. They published their findings in the journal eLife.
What are Human Papillomaviruses?
Human papillomaviruses (HPVs) are common viruses that cause a range of infections in people. Almost every individual in the world has been infected by one HPV type at some point. Health experts are concerned about HPV infections because of their relationship with various cancer types. When the virus infects a human cell, the integration of the viral genome into the cell's genome usually results in cellular changes.
As viruses, HPVs need to hijack cells to replicate copies. But to do that, they have to take over the cell's engine. The takeover inserts something and removes another, which reflects the alteration. One thing that can be removed is a function to prevent uncontrolled cellular replication. The takeover leads to two events: infected cells divide and viral genomes replicate. Thus, many strains of HPV are causative agents of cancer.
According to the US Centers for Disease Control and Prevention (CDC), a federal agency, there are six types of cancer induced by HPVs – anal, cervical, penile, vaginal, vulvar, and at the back of the throat. Both men and women can develop HPV-induced cancer if the infection persists. Over 120 HPV types are identified and the majority causes skin warts. But types 16 and 18 are high-risk HPVs capable of causing cancer. About 99% of global cervical cancer cases are found with high-risk HPV types. Out of those, around 50% are linked to type 16 and 70% are associated with both types 16 and 18.
As of August 2019, the annual cases of cancer-related HPV were 14,100 in men and 20,700 in women. Among several HPV-related cancer types, the type with the highest cases in men was cancer at the back of the throat at 11,300 annually. While the type with the highest cases in women was cervical cancer at 10,900 annually.
Cunning Move HPV Uses to Thwart Immune Response
In Germany, DFKZ scientists discovered how HPVs could evade the immune system. Using a bait, it could trick antibodies to bind to a false protein. This enabled HPVs to infect skin cells and increase the risk of malignancy. The cunning method was identified in specific cutaneous HPVs, such as HPV5 and HPV8.
The team investigated the mechanism based on known literature of HPVs avoiding innate immunity. Experiments conducted on specific mouse species showed that the viruses could even dodge adaptive immunity, which involves antibodies. HPV5 and HPV8 could be found on the skin as causative agents of natural infections. These HPV types do not spread sexually but could be passed down from mothers to their babies. Hence, a household could share the same HPV types.
Normally, the cutaneous HPVs do not persist when the immune system successfully conquer them. However, the viruses could persist depending on several factors like genetic disposition, exposure to ultraviolet light, and strength of the immune system. If the pathogens were not overcome, they could infect skin cells and create new copies when those cells divide. The situation could lead to skin changes or squamous cell carcinoma.
To learn how skin HPVs could dodge the immune system, Mastomys coucha mice were used to mimic events in the human skin. These mice could be infected by cutaneous HPVs after birth. Their immune system could also generate antibodies against the viruses. Scientists infected the mice with HPVs and exposed them to UV radiation. The animals became more prone to squamous cell carcinoma.
Results showed that the mice produced antibodies for two viral proteins of viral particles called capsids. The antibodies against L1 and L2 proteins could prevent and neutralize the viruses. But a close examination revealed that the viruses could generate a longer version of the L1. The longer version would not form the capsids. It would only serve as a bait to attract antibodies and protect the real L1 protein.
And finally, the team observed how the immune system reacted to the fake protein. Antibodies designed for L1 attached themselves to the longer version. The immune system detected the fake protein as a threat and created more antibodies for it. Eventually, the immune system realized that the longer version was a hoax. But it took several months before the real protein was identified. By that time, the viruses already spread to many host cells.
"In both rodents and humans, in almost all HPV types that can cause cancer, the L1 gene is designed such that a longer version of the protein can be produced. This is also true for high-risk HPV types such as HPV16 and HPV18, which can cause cervical cancer. It, therefore, appears to be a common mechanism that enables the viruses to replicate and spread efficiently during the early stage of infection," said Daniel Hasche, a senior author of the study and supervising scientist of the team.
The findings could explain why HPVs persist in human communities. Even people with a relatively strong immune system might be susceptible to the trick. While the team did not mention a possible solution, their discovery of the sly method could be utilized by future research in HPV. Perhaps other researchers could formulate compounds to stop the generation of the fake protein.
Right now, the most effective way to avoid HPV infection and HPV-related cancers is vaccination. The overall efficacy of HPV vaccines is over 95%, and only a small number of people develop severe adverse reactions. A common severe adverse reaction to the vaccine is anaphylaxis.