HIV Virus Discovered To Have A Secretive Transport Function

Human Immunodeficiency Virus (HIV) Discovered To Have A Secretive Transport Function | The Lifesciences Magazine

The virus that causes AIDS, Human Immunodeficiency Virus (HIV), infects about one million people globally every year. The virus needs to sneak its genetic material into the cell nucleus and integrate it into a chromosome in order to replicate and spread the infection. Its capsid has now been found to have developed into a molecular transporter by research teams led by Thomas Schwartz at MIT and Dirk Görlich at the Max Planck Institute for Multidisciplinary Science. Consequently, it has the ability to directly cross a critical barrier that typically shields the cell nucleus from viral intruders. This method of smuggling prevents anti-viral sensors in the cytoplasm from seeing the viral genome.

Though we now have treatments that successfully contain the infection, there is still no cure for AIDS, which was first linked to the human immunodeficiency virus (HIV) forty years ago. The virus replicates and multiplies by infecting specific immune cells and taking over their genetic programming. The subsequent virus generation is then produced by the infected cells until they are ultimately eliminated. The severe loss of immune cells, which typically combat viruses and other infections, is the cause of the immunodeficiency symptoms associated with AIDS.

Human immunodeficiency virus (HIV) must sneak its genetic material past cellular defence mechanisms and into the cell nucleus in order to utilise the resources of the host cell. But the nucleus is protected very carefully. Its nuclear membrane stops macromolecules from escaping uncontrollably and undesired proteins or dangerous viruses from entering the nucleus. Nevertheless, because the barrier is not completely sealed, some proteins can slip through.

The nuclear envelope has thousands of microscopic nuclear pores that act as a conduit. Importins and exportins, molecular transporters that seize cargoes with functional molecular “passcodes” and transfer them through the nuclear pore channel, assist them in managing these transport activities. These pores become one of nature’s most effective sorting and transport mechanisms thanks to a “smart” substance.

Human Immunodeficiency Virus (HIV) Virus Found to Possess Hidden Transport Ability

Sorting “smart” in the nuclear pore

The FG phase is a “smart” substance that is impermeable to most macromolecules and has a jelly-like consistency. It clogs the nuclear pore channel and fills it. However, importins and exportins can pass through because they have surfaces designed to let them to slide through a FG phase.

In the FG phase, the border control of the cell occurs milliseconds faster than usual. Its transport capacity is also quite high; a single nuclear pore has the ability to move up to 1,000 transporters via its channel in a single second. This high traffic density does not break the barrier of nuclear pores, which continues to prevent undesired border crossings. Human immunodeficiency virus (HIV), however, undermines this security.

Genetic Material Trafficked

“The HIV genome is contained in a capsid. According to recent data, the genome remains within the capsid both during the nuclear pore passage and until it enters the nucleus. However, Thomas Schwartz from MIT notes that there is a size issue. The width of the core pore channel is 40–60 nanometers. With its diameter of roughly 60 nanometers, the capsid could barely fit through the opening. However, a transporter layer that adds at least 10 nanometers would still cover a typical cellular cargo. At 70 nanometers in width, the HIV capsid would be too large to fit through a nuclear pore.

Nevertheless, cryo-electron tomography has shown that the HIV capsid gets into the nuclear pore. But how this happens has been so far a mystery in HIV infection.”

Dirk Görlich, Max Planck Director

Disguise as a molecular carrier

Now, he and Schwartz have figured out how the virus gets around its size issue—a complex molecular adaption, to be exact. “The HIV capsid has developed into a transporter with a surface like that of an importin. It can pass through the nuclear pore’s FG phase in this manner. Thus, the Human immunodeficiency virus (HIV) capsid may evade the defence system that stops viruses from entering the cell nucleus and enter the nuclear pore without aiding transporters,” the biochemist adds.

His group has been successful in simulating FG stages in the lab. One of the study’s founding authors, Liran Fu, notes that “under the microscope, FG phases appear as micrometer-sized spheres that completely exclude normal proteins, but virtually suck up the human immunodeficiency virus (HIV) capsid with its enclosed contents.” The work is currently available in the journal Nature. The capsid is drawn into the nuclear pore channel in a similar manner. Even after eliminating every cellular transporter, this still occurs.”

The HIV capsid is essentially different from other transporters that have been investigated and that pass through nuclear pores in one regard: it fully encapsulates its cargo, shielding its genomic payload from anti-viral sensors in the cytoplasm. By using this ruse, the genetic material of the virus can get through the cell’s defence mechanism without being detected and eliminated. “This makes it another class of molecular transporters alongside importins and exportins,” Görlich points out.

Many concerns remain unsolved, including where and how the contents of the capsid are released by disintegration. Nonetheless, the discovery that the capsid functions as a transporter akin to importin may one day be utilised to improve AIDS treatments.

Also Read: HIV: The Dusseldorf Patient Becomes the 5th Person to be Cured of HIV

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