AIDS was first reported by the CDC in 1981, and in 1983, scientists identified human immunodeficiency virus (HIV) infection as the cause of AIDS. Today, more than 40 years later, we have effective treatments and controls for the HIV, but there is still no cure for AIDS.
HIV infects and hijacks the CD4+ T cells of the immune system to replicate and multiply its own genetic material. The symptoms of immunodeficiency in AIDS patients are caused by the infection and attack of CD4+ T cells by HIV, resulting in a massive loss of these immune cells.
In order to replicate and spread, HIV must "smuggle" its genetic material into the cell nucleus and integrate it into the chromosomes. However, the nucleus is tightly protected by the nuclear membrane, which prevents the entry of unwanted proteins or viruses and the uncontrolled escape of macromolecules. But the nuclear membrane is not completely sealed. It is covered with thousands of tiny nuclear pores that regulate the movement of specific molecules in and out of the nucleus with the help of nuclear transporter proteins and a single nuclear pore can transport up to 1,000 transporter proteins per second.
Cryo-electron microscopy tomography shows that the HIV capsid enters the nucleus through the nuclear pore, but there is a size issue here. The central aperture of the nuclear pore is 40–60 nanometers in diameter, and the HIV capsid encapsulating the viral genome is 60 nanometers in diameter, which increases by at least another 10 nanometers to 70 nanometers when it binds to the transporter proteins, which is far too large for the nuclear pore. How the HIV capsid enters the nucleus through the nuclear pore remains a mystery.
On January 24, 2024, the Max Planck Institute, in collaboration with the Massachusetts Institute of Technology, published a research paper in Nature entitled "HIV-1 capsids enter the FG phase of nuclear pores like a transport receptor".
The study found that the HIV capsid has evolved into a nuclear transport protein that breaks through the critical barrier protecting the nucleus from viral invasion and crosses the nuclear pores into the nucleus without relying on the nuclear transport protein. Because the HIV genome is completely encapsulated by the capsid, this also allows the HIV genome to escape recognition by antiviral sensors in the cytoplasm of human cells, bypassing the cell's viral defenses and "smuggling" its own genetic material into the nucleus, where it can be further integrated into the chromosomes.
The nuclear pore complex (NPC) is constructed from about 30 different nuclear pore proteins (Nups), including about 10 so-called FG-Nups, which anchor barrier-forming phenylalanine-glycine (FG) repeat domains to the NPC scaffold in the form of a gel, also known as the FG phase, that fills and blocks the nuclear pore, allowing only the nuclear export and nuclear import proteins to pass through.
In this study, the team found that the HIV capsid has evolved into a transporter protein with a nuclear import protein-like surface so that it can slip through the FG phase of the nuclear pore. As a result, the HIV capsid can enter the nucleus through the nuclear pore without the help of a transporter protein, bypassing the protective mechanisms that prevent the virus from invading the nucleus.
The team also successfully replicated the FG phase in the laboratory. Under the microscope, the FG phase appears as micrometer-sized spheres that are able to completely block the entry of normal proteins but are able to adsorb the HIV capsid and its enclosed genome so that the capsid is translocated into the nuclear pore channel. This can occur even when all the cell's transporter proteins are removed, further suggesting that the HIV capsid is itself a class of nuclear transporter proteins.
In a way, the HIV capsid is fundamentally different from previously studied nuclear transporter proteins that pass through the nuclear pore: the HIV capsid completely encapsulates its cargo (the HIV genome), which allows the HIV genome to be unrecognized by antiviral sensors in the cytoplasm of the human cell, bypassing the cell's viral defenses and "smuggling" its genetic material into the nucleus.
The team says there are still many questions to be answered, such as where and how the HIV capsid breaks down and releases the genome. The study's observation that the HIV capsid is a transport protein similar to nuclear import proteins may help develop better AIDS treatments.
Note:Our consulting editor Jessica Kroner brings exclusive images of Afghan refugees who crossed Pakistan through the Chaman border.
Unfortunately, they were turned back by the Pakistani authorities citing lack of documents and their whereabouts are unknown since then.
Humanitarian agencies across the world should take note of the crisis in making and develop a sustainable mechanism to prevent another refugee crisis.
The Taliban’s occupation of Afghanistan overthrew the elected democracy and installed itself in Kabul, drawing concerns from the international community .
The Taliban’s violence especially against women and ethnic minorities instilled a sense of fear that opened yet another chapter of the refugee crisis.
The sight of women and children crossing into the Iranian and Pakistani border was deeply disturbing.Among them, I got a chance to cover the plight of some families that fled Kunduz, a city in northern Afghanistan.
