Viruses are mostly known for causing diseases, but a recent study from Harvard Medical School identifies a type of virus that could be more ‘friend’ than ‘foe’. In a provocative take, Harvard scientists suggest that Beta human papillomavirus might protect us from skin cancer rather than causing it.1
When the sun is shining, we are drawn to the outside. The sun boosts our mood, energizes us and gives some of us that lovely summer glow, but while soaking up rays has a positive effect on our bodies and minds, too much solar exposure can be harmful. UV radiation damages our skin cells, causing them to age faster and, in the worst case, transform into cancerous cells. While mindful sun exposure and proper protection can reduce the risk of skin cancer, scientists have discovered that we might get additional help from an unexpected ally: viruses.
Beta human papilloma viruses are less pathogenic than other members of the papilloma virus family. They hang out in our skin cells quietly living their lives, occasionally causing a verruca or maybe triggering psoriasis. Unlike their mucosal epithelium dwelling cousins, alpha HPV, they don’t trigger cancer or outbreaks of warts. What they can do, scientists have recently discovered, is to help our immune cells to recognize when epithelial cells are in danger of becoming cancerous.
The ways in which sunlight can harm our skin cells and lead to skin cancer are well studied2. Ultra Violet radiation injures DNA in our skin cells, which can impair the cells’ functions and progress to cancer. Of course, the body has means to prevent that fate; for example, it can mend the DNA damage. If the harm is beyond repair, the cell initiates a suicide programme before the damage can get out of hand and develop into cancer.
P53, is one of the most important ‘tumour suppressor’ genes to be identified. p53 protein plays an essential role in cellular responses to DNA damage. When DNA is injured, p53 gets to work either by ensuring timely DNA repairs or cell death. Unfortunately, if the gene that encodes p53 itself is affected and the protein does not function as intended, the cell becomes vulnerable to cancer-causing changes. In the lab when a scientist switches off the p53 gene in a cell, they continue to replicate themselves even in situations where they shouldn’t – just like in cancer cells.
This tumour preventing protein is essential to fighting cancer – in as many as 90% of cases of the second most common skin cancer–cutaneous squamous cell carcinoma, doctors find that the patient has a faulty p53 gene.
Viruses generally have a bad reputation because they can cause some of the worst diseases known to humankind. It might surprise you, then, that some viruses can help us fight illness and prolong our lives.
In a paper published earlier this year in Cancer Cell, a prestigious research journal, Harvard medical school investigators proposed that the beta human papillomaviruses (beta HPV) could prevent skin cancer. That’s right, this viral vanguard alerts the body’s immune system to eliminate cells damaged by UV radiation before they become cancerous.
So how could a common skin virus help our immune cells spot signs of UV damage?
Historically, pathologists and cell biologists have noticed that beta Human Papillomavirus viruses often turned up in skin cancer lesions. At first, cancer doctors wondered whether the Beta HPV infection was, like alpha HPV in the mouth or cervix, triggering cancerous changes in the cells. In 2019, however, cancer researchers noted that hairless mice infected with the virus were actually less likely to develop skin cancer.4 This 20251 study digs deeper into these results asking the question, what’s going on inside the cells?
The team started off by going back to these mysterious mice. Just what was causing the protective effect?
Mice are also vulnerable to skin cancer after extensive UV exposure, and just like in humans, a mutation of its p53 protein sets skin cells on a path to becoming cancerous. The researchers infected half of the mice with the mouse version of the beta papillomavirus and then blasted infected mice and their uninfected brothers and sisters with daily doses of UV radiation. They used a special type of hairless mouse for two reasons; firstly it makes it easier for us to see when the mouse develops a lesion, and secondly, mouse fur blocks UV radiation. That saves a lot of time spent on shaving if you can’t get hold of bald ones!
After several months of synthetic sunburn, the mice started to develop skin lesions that showed signs of early skin cancer – a missing or faulty p53. When the team compared the precancerous cells from Beta MPV infected mice to uninfected mice, they found an important molecular mismatch.
The researchers noticed that the mice infected with the virus had much smaller precancerous lesions than did their infected siblings. Just like in nature, faulty or missing p53 cancer fighting proteins had caused the precancerous changes. When the team infected another set of mice with a different skin virus, they did not see the same effect – all the mice had similar sized precancerous lesions, and all of them had missing or faulty p53. This signals something special about the beta MPV in particular, that stopped the cells lacking p53 from multiplying.
Taking a closer look at the differences between precancerous cells infected with the virus and nearby cells, the researchers noted that if cells had malfunctioning p53, they contained far higher amounts of papillomavirus than cells with a normal version of p53.
When the researchers examined the two sets of mice’s immune response they found that the virus infected precancerous skin patches attracted immune cells faster and more effectively than skin lesions that did not have beta MPV in them. The immune cells killed the damaged skin cells before they could become cancerous.
Briefly, they discovered that if they infected a mouse with beta MPV, when UV damage caused p53 to fail, the virus took advantage. Once the beta MPV infection hit a certain level, it triggered the cell to send out SOS signals to the immune system. Cell killing white blood cells answered the call, with the task of destroying cells infected with the virus. Luckily for the mouse, destroying the virus also killed the precancerous cells, stopping the tumour from growing.
If the body’s damage control by p53 fails, the papillomavirus steps in and alerts the immune system.
Of course, having discovered this immunogenic effect in mice, the next step was to see if it works in humans3.
The skin cancer scientists collected skin samples from people’s faces and torsos. Since our faces get more sun exposure, on inspection they found more signs of UV damage there. Interestingly, the sun-exposed facial skin had more beta Human Papillomavirus compared to skin from the torso. And here is another twist: precancerous patches of skin actually had less beta HPV than the surrounding skin. It seems as if those patches became cancerous because they did not have enough beta HPV to call in the immune system for backup.
The research on the relation between human skin cells and beta Human Papillomavirus is still in its infancy. The exact molecular mechanism of this ‘viral sunscreen’ is not fully clear.
Nevertheless, these results highlight that viruses are not always villains – they can be unexpected allies. As scientists continue to explore this fascinating relationship between us and viruses, we might discover that they are more than just pests. Some of them could be tiny, unsung heroes helping us stay healthy.
References:
1: Son HG, Ha DT, Xia Y, Li T, Blandin J, Oka T, Azin M, Conrad DN, Zhou C, Zeng Y, Hasegawa T, Strickley JD, Messerschmidt JL, Guennoun R, Erlich TH, Shoemaker GL, Johnson LH, Palmer KE, Fisher DE, Horn TD, Neel VA, Nazarian RM, Joh JJ, Demehri S. Commensal papillomavirus immunity preserves the homeostasis of highly mutated normal skin. Cancer Cell. 2024 Dec 7:S1535-6108 (24) 00448-3. doi: 10.1016/j.ccell.2024.11.013
2: Carvalho C, Silva R, Melo TMVDPe, Inga A, Saraiva L. P53 and the Ultraviolet Radiation-Induced Skin Response: Finding the Light in the Darkness of Triggered Carcinogenesis. Cancers. 2024; 16(23):3978. https://doi.org/10.3390/cancers16233978
3: Offord C. Common virus may help protect skin against Sun damage. 2024 Dec 12. Common virus may help protect skin against Sun damage | Science | AAAS
4. Strickley JD, Messerschmidt JL, Awad ME, et al. Immunity to commensal papillomaviruses protects against skin cancer. Nature. 2019;575 (7783):519–522. doi:10.1038/s41586-019-1719-9
Viruses are mostly known for causing diseases, but a recent study from Harvard Medical School identifies a type of virus that could be more ‘friend’ than ‘foe’. In a provocative take, Harvard scientists suggest that Beta human papillomavirus might protect us from skin cancer rather than causing it.1 When the sun is shining, we are drawn to the outside. The sun boosts our mood, energizes us and gives some of us that lovely summer glow, but while soaking up rays has a positive effect on our bodies and minds, too much solar exposure can be harmful. UV radiation damages our skin cells, causing them to age faster and, in the worst case, transform into cancerous cells. While mindful sun exposure and proper protection can reduce the risk of skin cancer, scientists have discovered that we might get additional help from an unexpected ally: viruses. Beta human papilloma viruses are less pathogenic than other members of the papilloma virus family. They hang out in our skin cells quietly living their lives, occasionally causing a verruca or maybe triggering psoriasis. Unlike their mucosal epithelium dwelling cousins, alpha HPV, they don’t trigger cancer or outbreaks of warts. What they can do, scientists have recently discovered, is to help our immune cells to recognize when epithelial cells are in danger of becoming cancerous. The ways in which sunlight can harm our skin cells and lead to skin cancer are well studied2. Ultra Violet radiation injures DNA in our skin cells, which can impair the cells’ functions and progress to cancer. Of course, the body has means to prevent that fate; for example, it can mend the DNA damage. If the harm is beyond repair, the cell initiates a suicide programme before the damage can get out of hand and develop into cancer. P53, is one of the most important ‘tumour suppressor’ genes to be identified. p53 protein plays an essential role in cellular responses to DNA damage. When DNA is injured, p53 gets to work either by ensuring timely DNA repairs or cell death. Unfortunately, if the gene that encodes p53 itself is affected and the protein does not function as intended, the cell becomes vulnerable to cancer-causing changes. In the lab when a scientist switches off the p53 gene in a cell, they continue to replicate themselves even in situations where they shouldn’t – just like in cancer cells. This tumour preventing protein is essential to fighting cancer – in as many as 90% of cases of the second most common skin cancer–cutaneous squamous cell carcinoma, doctors find that the patient has a faulty p53 gene. Viruses generally have a bad reputation because they can cause some of the worst diseases known to humankind. It might surprise you, then, that some viruses can help us fight illness and prolong our lives. In a paper published earlier this year in Cancer Cell, a prestigious research journal, Harvard medical school investigators proposed that the beta human papillomaviruses (beta HPV) could prevent skin cancer. That’s right, this viral vanguard alerts the body’s immune system to eliminate cells damaged by UV radiation before they become cancerous. So how could a common skin virus help our immune cells spot signs of UV damage? Historically, pathologists and cell biologists have noticed that beta Human Papillomavirus viruses often turned up in skin cancer lesions. At first, cancer doctors wondered whether the Beta HPV infection was, like alpha HPV in the mouth or cervix, triggering cancerous changes in the cells. In 2019, however, cancer researchers noted that hairless mice infected with the virus were actually less likely to develop skin cancer.4 This 20251 study digs deeper into these results asking the question, what’s going on inside the cells? The team started off by going back to these mysterious mice. Just what was causing the protective effect? Mice are also vulnerable to skin cancer after extensive UV exposure, and just like in humans, a mutation of its p53 protein sets skin cells on a path to becoming cancerous. The researchers infected half of the mice with the mouse version of the beta papillomavirus and then blasted infected mice and their uninfected brothers and sisters with daily doses of UV radiation. They used a special type of hairless mouse for two reasons; firstly it makes it easier for us to see when the mouse develops a lesion, and secondly, mouse fur blocks UV radiation. That saves a lot of time spent on shaving if you can’t get hold of bald ones! After several months of synthetic sunburn, the mice started to develop skin lesions that showed signs of early skin cancer – a missing or faulty p53. When the team compared the precancerous cells from Beta MPV infected mice to uninfected mice, they found an important molecular mismatch. The researchers noticed that the mice infected with the virus had much smaller precancerous lesions than did their infected siblings. Just like in nature, faulty or missing p53 cancer fighting proteins had caused the precancerous changes. When the team infected another set of mice with a different skin virus, they did not see the same effect – all the mice had similar sized precancerous lesions, and all of them had missing or faulty p53. This signals something special about the beta MPV in particular, that stopped the cells lacking p53 from multiplying. Taking a closer look at the differences between precancerous cells infected with the virus and nearby cells, the researchers noted that if cells had malfunctioning p53, they contained far higher amounts of papillomavirus than cells with a normal version of p53. When the researchers examined the two sets of mice’s immune response they found that the virus infected precancerous skin patches attracted immune cells faster and more effectively than skin lesions that did not have beta MPV in them. The immune cells killed the damaged skin cells before they could become cancerous. Briefly, they discovered that if they infected a mouse with beta MPV, when UV damage caused p53 to fail, the virus took advantage. Once the beta MPV infection hit a certain level, it triggered the cell to send out SOS signals to the immune system. Cell killing white blood cells answered the call, with the task of destroying cells infected with the virus. Luckily for the mouse, destroying the virus also killed the precancerous cells, stopping the tumour from growing. If the body’s damage control by p53 fails, the papillomavirus steps in and alerts the immune system. Of course, having discovered this immunogenic effect in mice, the next step was to see if it works in humans3. The skin cancer scientists collected skin samples from people’s faces and torsos. Since our faces get more sun exposure, on inspection they found more signs of UV damage there. Interestingly, the sun-exposed facial skin had more beta Human Papillomavirus compared to skin from the torso. And here is another twist: precancerous patches of skin actually had less beta HPV than the surrounding skin. It seems as if those patches became cancerous because they did not have enough beta HPV to call in the immune system for backup. The research on the relation between human skin cells and beta Human Papillomavirus is still in its infancy. The exact molecular mechanism of this ‘viral sunscreen’ is not fully clear. Nevertheless, these results highlight that viruses are not always villains – they can be unexpected allies. As scientists continue to explore this fascinating relationship between us and viruses, we might discover that they are more than just pests. Some of them could be tiny, unsung heroes helping us stay healthy. References: 1: Son HG, Ha DT, Xia Y, Li T, Blandin J, Oka T, Azin M, Conrad DN, Zhou C, Zeng Y, Hasegawa T, Strickley JD, Messerschmidt JL, Guennoun R, Erlich TH, Shoemaker GL, Johnson LH, Palmer KE, Fisher DE, Horn TD, Neel VA, Nazarian RM, Joh JJ, Demehri S. Commensal papillomavirus immunity preserves the homeostasis of highly mutated normal skin. Cancer Cell. 2024 Dec 7:S1535-6108 (24) 00448-3. doi: 10.1016/j.ccell.2024.11.013 2: Carvalho C, Silva R, Melo TMVDPe, Inga A, Saraiva L. P53 and the Ultraviolet Radiation-Induced Skin Response: Finding the Light in the Darkness of Triggered Carcinogenesis. Cancers. 2024; 16(23):3978. https://doi.org/10.3390/cancers16233978 3: Offord C. Common virus may help protect skin against Sun damage. 2024 Dec 12. Common virus may help protect skin against Sun damage | Science | AAAS 4. Strickley JD, Messerschmidt JL, Awad ME, et al. Immunity to commensal papillomaviruses protects against skin cancer. Nature. 2019;575 (7783):519–522. doi:10.1038/s41586-019-1719-9
