Hepatitis C is an infectious disease affecting over 70 million people across the world.

It
increases the risk of developing severe liver cancer or cirrhosis condition. Apparently,
there is no vaccine existing to curb the infection. The reason is HCV infects only certain
species such as Humans & Chimpanzees. This makes the study of HCV difficult in the
laboratory.

In light of this, many scientists were working ahead to understand the underlying
factors involved in the replication of the Hepatitis C virus. A recent study done by the
researchers at Princeton University found that certain difference in liver cell proteins
can impact HCV replication in mice & humans. The research is published in the journal
of eLife.

The researchers were focussed on understanding the requirements of the virus to

replicate in humans. So that an animal model can be developed to help study the virus
and develop a vaccine against it.

The Science Behind It

Scientist genetically engineered mice, which once infected with HCV are able to produce
human proteins. These human proteins allow the virus to enter into the liver cells &
infect them causing liver cancer or cirrhosis. However, in the case of mice the immune
system has to be made compromised to allow the HCV to replicate, otherwise, it won’t.
Scientist focussed themselves to a protein called cyclophilin A. This protein is important
in human for HCV to multiply & replicate within the liver cells. It was found that the
mouse version of this protein is very less efficient in promoting the replication of the
virus in comparison to the human cyclophilin A.

A model of the “humanized” version of mouse cyclophilin A shows the mutated parts of
the protein as green sticks, and the protein’s active site as purple sticks. (CREDIT
Credit: Jenna Gaska, Princeton University)

Thus, scientist mutated the mouse version of cyclophilin A to resemble more like human
cyclophilin A. These changes improved the viral replication in mouse at levels similar to
human cyclophilin A. When this humanized version of protein was inserted into liver
cancer cells, which normally does not allow HCV replication, there was a rise in HCV
replication.

Additionally, the researchers also tried to check the replication response with other
mutant proteins involved in HCV replication. It was found that cyclophilin A is majorly
responsible for viral replication. However, the intensity of replication was not the same
as in humans. This indicated that there are other protein factors which play a crucial
role in viral replication within the liver cells.

“Identifying these factors will be the subject of our future work, which we hope
will ultimately lead to an immunocompetent mouse model for studying HCV
and developing an effective vaccine,” said Ploss, the author.

Way Ahead

The study is very interesting & important that can help in the future to curb the menace
of the Hepatitis C virus. The research paves the way for the future development of
animal models to produce a vaccine for the disease. Understanding the role of
cyclophilin A promoting viral replication put forward many opportunities for researcher
to dissect the underlying mechanism of cyclophilin A-dependent HCV infection.