The wrong track: How papillomaviruses trick the immune system

Date:
August 4, 2020
Source:
German Cancer Research Center (Deutsches Krebsforschungszentrum,
DKFZ)
Summary:
Specific antibodies protect us against viral infections - or do they
not? Researchers studied the immune response to papillomaviruses
in mice and discovered a hitherto unknown mechanism by which
the pathogens outwit the immune system: At the beginning of the
infection cycle, they produce a longer version of a protein that
surrounds the viral genome. The body produces antibodies against
this protein, but they are not effective in fighting the pathogen.



FULL STORY ========================================================================== Specific antibodies protect us against viral infections -- or do they not? Researchers at the German Cancer Research Center (DKFZ) studied the
immune response to papillomaviruses in mice and discovered a hitherto
unknown mechanism by which the pathogens outwit the immune system: At
the beginning of the infection cycle, they produce a longer version of
a protein that surrounds the viral genome. The body produces antibodies
against this protein, but they are not effective in fighting the pathogen.


==========================================================================
The human immune system has a wide variety of defense strategies to
protect the body against pathogens, one of which involves producing
antibodies to fight viruses and bacteria. Over time, however, these
pathogens have developed elaborate ways of escaping the immune system.

Scientists are already aware of some of these strategies. In human papillomaviruses (HPV), however, up until now they have only known about
such strategies in innate, already present immunity and not in adaptive immunity, which does not develop until pathogens enter the body and is associated with the production of antibodies.

Frank Ro"sl and his co-workers from DKFZ under the supervision of
Daniel Hasche have now discovered a new mechanism by which cutaneous papillomaviruses (specific to the skin) trick the immune system.

Certain cutaneous HPV, such as HPV5 and HPV8, occur as natural infections
on the skin. They are not sexually transmitted, but are passed on from the mother to the newborn child. Thus, family members are usually colonized
with the same HPV types. An infection normally goes unnoticed, because
the body is able to overcome it. Depending on the individual status of
a person's immune system, their genetic predisposition, age, and other
external factors such as UV radiation, however, certain cutaneous HPV
types are able to stimulate cell division in their host cells. This
leads to skin changes and in rare cases to development of a squamous
cell carcinoma, also known as fair-skin cancer.

The experiments were conducted in a particular mouse species, Mastomys
coucha, which, like humans, can become infected with cutaneous
papillomaviruses shortly after birth and produce specific antibodies
against the virus. In combination with UV radiation, infected animals
are more likely to develop squamous cell cancer.

The animals' immune system produces antibodies against the two viral
proteins L1 and L2 that make up the virus particles, also called
capsids. These antibodies can prevent the viruses from entering the host
cells and thus neutralize the virus. However, the experiments carried
out by the DKFZ scientists showed that besides the normal L1 protein,
the viruses also produce a longer version. The latter is not able to
actually take part in forming the viral capsid. Instead, it acts as a
kind of bait against which the immune system directs its response and
produces specific antibodies.

However, the scientists were able to demonstrate that these antibodies
are not effective in fighting the papillomavirus. Instead of neutralizing
the infectious pathogen through binding to L1, the antibodies merely bind
the nonfunctional protein used as bait. While the immune system is busy producing these non-neutralizing antibodies, the virus can continue to replicate and spread throughout the body. It take several more months
before neutralizing antibodies are produced that target the normal L1
protein and ultimately the infectious viruses themselves.

"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," Daniel Hasche explained. "The fact
that antibodies against papillomaviruses can be detected is therefore
not necessarily associated with protection against infection. This will
need to be taken into account in future when evaluating and interpreting epidemiological studies," Frank Ro"sl added.


========================================================================== Story Source: Materials provided by
German_Cancer_Research_Center_(Deutsches
Krebsforschungszentrum,_DKFZ). Note: Content may be edited for style
and length.


========================================================================== Journal Reference:
1. Yingying Fu, Rui Cao, Miriam Scha"fer, Sonja Stephan, Ilona
Braspenning-
Wesch, Laura Schmitt, Ralf Bischoff, Martin Mu"ller, Kai Scha"fer,
Sabrina E Vinzo'n, Frank Ro"sl, Daniel Hasche. Expression of
different L1 isoforms of Mastomys natalensis papillomavirus as
mechanism to circumvent adaptive immunity. eLife, 2020; 9 DOI:
10.7554/eLife.57626 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/08/200804111526.htm

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