The capsid is the complex outer layer surrounding HIV’s genetic material. It is primarily used for protection, though also plays essential roles in early stage replication and transport inside the virus. A huge hurdle in HIV research has been figuring out how this protective protein is structured.

Utilizing toxins

Imaging difficulties have arisen for decades due to the unstable state of the capsid, with small disturbances affecting its natural conical shape and structure. High resolution analyses have been too invasive to successfully image the structure… until now.

The team that overcame the issue is based at the University of Oxford. They conducted their research at Diamond’s electron Bio-Imaging Centre (eBIC), the UK’s national cryo-electron microscopy facility. The group cleverly invented a new technique using pore-forming toxins, replacing the steps which cause changes to the capsid. They managed to finally uncover this structure in HIV on its own, as well as how it interacted with other molecules in the environment. Understanding how these elements keep the capsid in its stable state opens possible avenues for targeted viral treatments.

Capturing the structure

Traditionally, humans have used light to capture images. This is how our everyday cameras work, but scientists figured out that replacing this light with electrons creates high-resolution microscopes, where tiny structures can be observed. It is electrons’ smaller wavelength compared to the light that gives them this power of capturing smaller detail. The paper, published in Science Advances, utilized these particles to image the microscopic structure in a process named electron tomography. After this step, the picture of the sample created was refined for accuracy using a technique called subtomogram averaging.

Why is this research important?

“Despite the global efforts to combat HIV/AIDS and the achievement of antiviral treatments, there are still approximately 38 million people with HIV/AIDS with no complete cure so far,” said lead author Peijun Zhang. This research stands as a blueprint for creating new therapies to target the virus. Hopefully from this understanding, scientists will be able to find a cure for not just HIV, but other viral infections.

Source study: Science Advances – Structure of native HIV-1 cores and their interactions with IP6 and CypA