Infection by the human immunodeficiency virus 1 (HIV-1) significantly damages our immune system, leading to the development of acquired immunodeficiency syndrome or AIDS. While many researchers have spent years studying the HIV-1 life cycle, we still do not fully understand how HIV-1 enters our cell nucleus, a critical step for the virus to replicate. For one, HIV-1 is too large to just squeeze itself through our nuclear pores. The HIV-1 capsid (the shell of the virus) is 60 nm wide and the average width of a nuclear pore is 40 nm, with the largest pores being 60 nm. To put that into perspective, a human hair is 100 μm thick, making the largest pores almost 1000 times smaller! While the HIV-1 capsid by itself is small enough to fit through the largest pores, HIV-1 would still need to be coated by a 10 nm transporter layer to help push the cargo (in this case, HIV-1) through the pore. This additional layer would make HIV-1 way too large. However, researchers at the Max Planck Institute and MIT may have discovered the solution to this puzzle.

Using electron microscopy and cellular assays simulating an HIV infection, the researchers determined that an HIV-1 capsid-like particle (a particle of a similar shape and size as HIV-1 but not actually the virus itself) could traverse nuclear pores effectively without the help of a transporter layer. This finding suggests that the HIV-1 capsid may act less like typical cargo and more like the transporter layer itself, which easily enters and transverses pores. Without the extra 10 nm from a transporter layer, the HIV-1 capsid would be just small enough to fit through the largest nuclear pores. Mystery potentially solved!

While there are currently effective treatments for AIDS, there is still no permanent cure. Therefore, it is critical that we continue studying the HIV-1 life cycle to develop ways to halt and possibly even eradicate the virus. For instance, the researchers here have found that capsid interactions with the nuclear pores are required for HIV-1 infection, so a future treatment that disrupts that interaction could show therapeutic potential. That said, further research is needed to prove that these results also apply to the actual virus, and not just the capsid-like particles.

This study was led by researchers at the Department of Cellular Logistics and the Department of Meiosis at the Max Planck Institute for Multidisciplinary Sciences & the Department of Biology at the Massachusetts Institute of Technology, including corresponding authors Thomas Schwartz and Dirk Görlich.

Managing Correspondent: Jenny Kim

Press Article: HIV’s Capsid Transports the Viral Genome into the Cell’s Nucleus (GEN)

Original Journal Article: HIV-1 capsids enter the FG phase of nuclear pores like a transport receptor (Nature)

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