Researchers uncover why monkeys resist HBV infection, revealing evolutionary adaptations. Why Monkeys Resist Hepatitis B: Insights for New Therapies | Technology Networks
1 Like
Hi @ MARIAN
This is the interesting research for HBV cure in the future . From this study , the mechanism of natural resistance of HBV infection in monkeys is due to the instability of HBV pre S1 surface protein binded with NTCP receptor of hepatocytes which contain arginine instead of lysine like human hepatocytes. The question is :If we can identify genome sequences that transcripts and translate NTCP protein receptors, can we use gene therapy like CRISPR based genetic engineering technology for gene editing that can change amino acids sequence from lysine of human to arginine like in monkey NTCP . This may be one possible option for the patients with HBV and HDV infection.
chul_chan
Chulapong Chanta MD. Pediatric
2 Likes
Great thought! The genome sequence of human NTCP gene has already been identified and cloned. In fact, the entire human genome has been sequenced many times. The problem with such a genome editing is at least two folds: First, somatic genome editing is almost impossible as all copies of the gene will need to be edited at least in all hepatocytes in the liver. Second, genome editing at the embryonic stage has been done in HIV receptor gene CRC5 to prevent HIV infection, but it was considered unethical and the Chinese lead investigator was jailed. Same concern with the HIV receptor, we don’t know if human NTCP gene is edited to become that of a monkey gene, what will be the consequences. Theoretically, if all human genes are replaced with that of monkey, we will become monkey 
3 Likes
Dear @MARIAN,
Thanks for raising this interesting paper.
To me, the idea around this is that macaques and humans are really similar and even their NTCP sequence is very similar. But even with this similarity there’s a key difference, HBV can infect humans but not macaques. This lets us know what is really important for the virus to get into a cell.
In the paper, the scientists were able to make the atomic structure of both the human and macaque NTCP to see how it interacted with HBV. They could also change bits of the macaque NTCP to look a bit more like the human NTCP to see how it behaved in cells in a petri dish. They found that it’s not just about getting the virus to bind to the receptor, but how the whole structure is stabilised after binding that is important for infection.
While this is pretty far from the clinic, this is important information to let us know better ways of targeting the entry of the virus and also to design better models of virus infection - which we can then go to use to develop better drugs.
Hope this helps,
Thomas
3 Likes