2023-08-11 08:36:30
How does HIV invade the cell nucleus? A team of researchers – including Italian scientists – has discovered a new route followed by the AIDS virus to reach its goal. A “protein pathway that appears to have a direct impact on disease and opens up a new area for potential drug development.” This is explained by the senior author of the study published in ‘Nature Communications’, Aurelio Lorico, professor of Pathology and interim Chief Research Officer at Touro University Nevada College of Osteopathic Medicine.
The researchers, including 3 scholars from the University of Palermo, have also identified three proteins necessary for the virus to carry out the invasion and have in turn synthesized molecules aimed at targeting one of these. A step forward in the direction that can lead to new treatments for AIDS (and not only). HIV infection requires the virus to enter a cell and gain access to the well-protected ‘fortress’ of the cell nucleus. Being able to conquer the nucleus is important for the virus, so that the viral components can be integrated into the DNA of the healthy cell. But how pathogens get past the protective membrane is not well understood and is a matter of debate.
The pathway identified by the study authors begins with HIV entering a cell wrapped within a membrane package, called an endosome. The virus-containing endosome pushes the protective nuclear membrane inward, forming an indentation known as the nuclear invagination, and then travels within this indentation to its inner tip, where the virus can then slide into the nucleus. The enemy is now ‘in house’ and can start the invasion.
For this operation to be successful, the scientists continue, 3 proteins must interact: Rab7 which is located on the endosome membrane, Vap-A which is on the nuclear membrane where the key step occurs, and the third, Orp3, which connects to the first two. Hence the hypothesis: targeting any of these proteins could stop the infection. The team thus synthesized and tested molecules that disrupt the interaction between proteins. Result: in the presence of these molecules, HIV replication does not take place.
This pathway for accessing the core is also likely involved in other diseases, experts suggest. “Our research is in a preclinical phase”, Lorico points out, but there are prospects for future developments: “It is probable that the new synthesized drugs may have therapeutic activity in AIDS, in other viral diseases and possibly in metastatic cancer and in other diseases in which nuclear transport is involved”. The team is also currently examining the role of the pathway in Alzheimer’s disease and metastasis from different cancer types. “There is a tremendous amount of work to be done to understand the full benefits of this research,” concludes Denis Corbeil, study co-lead author and research group leader at the Biotechnology Center at Dresden University of Technology in Germany.
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