Researchers uncover molecular mechanisms of rare skin disease

August 1, 2018, Rockefeller University
Keratinocyte skin cells are common targets of the beta subtype of human papilloma virus. This usually harmless infection causes skin disease in people with rare gene mutations. Credit: The Rockefeller University

Keratinocyte skin cells are common targets of the beta subtype of human papilloma virus. This usually harmless infection causes skin disease in people with rare gene mutations.[/caption]

You're probably infected with one or more subtypes of the —and, as alarming as that may sound, odds are you will never show any symptoms. The beta subtype of the , ß-HPV, is widespread in the general population and the least pathogenic; in fact, most carriers don't even know that they have it.

Yet, in people with the rare epidermodysplasia verruciformis (EV), some of these viruses cause lesions known as flat warts; later in life they can also cause to skin cancer.

Led by Rockefeller scientist Jean-Laurent Casanova, head of the St. Giles Laboratory of Human Genetics of Infectious Diseases, a group of researchers recently elucidated the molecular mechanisms that make people with EV vulnerable to ß-HPVs. In a new study, published in the Journal of Experimental Medicine, the scientists trace the disease to changes in a group of proteins that normally protect skin cells from the viruses.

Cracks in the armor

In patients with EV, ß-HPVs infect skin cells known as keratinocytes and provoke their proliferation. Searching for genetic causes of the disease, Casanova's team found that it is sometimes associated with mutations in a human gene coding for the protein CIB1.

They observed that individuals with CIB1 deficiency have symptoms identical to those with mutations to EVER1 or EVER2, two genes previously linked to EV. The researchers also noted that patients with EVER1 or EVER2 mutations have very low levels of CIB1, suggesting that the three proteins interact.

The scientists concluded that EVER1, EVER2, and CIB1 form a unit that, when functioning correctly, protects keratinocytes from ß-HPVs. If any part of this unit is compromised, however, the viruses are able to replicate and lead to pathological transformations of .

A flawed virus finds a hospitable host

ß-HPVs are, in a sense, defective: they fail to make two proteins, E5 or E8, which are produced by all other subtypes of HPVs and can occasionally cause common warts. Both E5 and E8 interact with CIB1. Without these proteins, Casanova says, ß-HPVs are no match for the CIB1-EVER1-EVER2 unit, which prevents them from harming cells.

Casanova posits that people with EV are vulnerable to ß-HPVs because their own genetic irregularities nullify those of the viruses. That is, the can compensate for their missing proteins because the corresponding human defense mechanism is awry.

"When people have in CIB1, EVER1 or EVER2, the ß-HPVs can promote the growth of keratinocytes—and can form warts and cancer—because there's nothing to stop them, even though they are intrinsically defective, lacking E5 and E8" he says.

Explore further: Mutation explains why some people are more vulnerable to viral brain infection

More information: Sarah Jill de Jong et al, The human CIB1–EVER1–EVER2 complex governs keratinocyte-intrinsic immunity to β-papillomaviruses, The Journal of Experimental Medicine (2018). DOI: 10.1084/jem.20170308

Related Stories

Mutation explains why some people are more vulnerable to viral brain infection

February 22, 2018
For previously healthy children, brain infections are rare. But about one out of every 10,000 people who are exposed to common viruses like herpes simplex or influenza will develop a potentially deadly disease, encephalitis.

New drug screening system could help speed development of a cure for HPV

February 9, 2017
Scientists have used genetic engineering techniques to develop a new system that could aid identification of potential drug targets and treatments for human papillomavirus (HPV) infection, according to a PLOS Pathogens study.

Scientists uncover potential mechanism for HPV-induced skin cancer

June 22, 2017
Scientists have identified a molecular pathway by which some types of human papilloma virus (HPV) might increase the risk of skin cancer, particularly in people with the rare genetic disorder epidermodysplasia verruciformis ...

Scientists design new skin cell culture technique to study human papillomavirus

March 1, 2018
A new cell culture strategy promises to illuminate the mysterious early stages of human papillomavirus (HPV) infection, according to research published in PLOS Pathogens by Malgorzata Bienkowska-Haba and colleagues at Louisiana ...

Recommended for you

PET scans to optimize tuberculosis meningitis treatments and personalize care, study finds

December 6, 2018
Although relatively rare in the United States, and accounting for fewer than 5 percent of tuberculosis cases worldwide, TB of the brain—or tuberculosis meningitis (TBM)—is often deadly, always hard to treat, and a particular ...

Silicosis is on the rise, but is there a therapeutic target?

December 6, 2018
Researchers from the CNRS, the University of Orléans, and the company Artimmune, in collaboration with Turkish clinicians from Atatürk University, have identified a key mechanism of lung inflammation induced by silica exposure, ...

Infectivity of different HIV-1 strains may depend on which cell receptors they target

December 6, 2018
Distinct HIV-1 strains may differ in the nature of the CCR5 molecules to which they bind, affecting which cells they can infect and their ability to enter cells, according to a study published December 6 in the open-access ...

Protecting cell powerhouse paves way to better treatment of acute kidney injury

December 6, 2018
For the first time, scientists have described the body's natural mechanism for temporarily protecting the powerhouses of kidney cells when injury or disease means they aren't getting enough blood or oxygen.

New study uncovers why Rift Valley fever is catastrophic to developing fetuses

December 5, 2018
Like Zika, infection with Rift Valley fever virus can go unnoticed during pregnancy, all the while doing irreparable—often lethal—harm to the fetus. The results of a new study, led by researchers at the University of ...

Study highlights potential role of bioaerosol sampling to address airborne biological threats

December 5, 2018
As a leading global city with a high population density, Singapore is vulnerable to the introduction of biological threats. Initiating an early emergency response to such threats calls for the rapid identification of the ...

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

celina12345
not rated yet Aug 01, 2018
I was cured of HIV with the used of natural herbs. My name is celina jolly and am from US. I love herbs so much. Most times, injection and drugs are just a waste of time. I was cured 8 months ago, i suffered from HIV for 13 yrs but with the help of Dr.Ogun herbal medicine, i was cured within few weeks of drinking the herbs he sent to me through courier delivery service. This same doctor also cured my Aunty from herpes, as soon as i heard she had herpes, i quickly refer her to Dr.Ogun and she was cured too after drinking his herbs.I have referred more than 15 persons to Dr.Ogun and they were all cured from their various illness. Have you taken herbs before?. You have spent so much money on drugs,injections,surgeries etc and yet you have no good result to show for it. Contact Dr. Ogun now, he is a herbalist doctor, i assured you of a cure if you drink his natural herbs. Dr.Ogun have herbs that cures Hiv, Herpes, etc contact DR.OGUN via email drogun62@gmail.com

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.