Researchers have identified the atomic structure of an apparatus that is key to HIV’s effort to integrate its genetic code into the DNA of a human cell and ultimately make new copies of itself.

Their findings about this machinery, known as the intasome, could help scientists develop improved antiretroviral (ARV) treatments that are less susceptible to drug resistance than today’s therapies.

The integrase strand transfer inhibitor (INSTI) class of ARVs targets the intasome. Despite the high potency of the drugs in this class, scientists are still limited in their understanding of how they work, not to mention how HIV develops resistance against them. They have developed a moderate, inferential understanding of the HIV intasome by studying the intasome of a similar, less complex retrovirus known as PFV. HIV’s intasome, meanwhile, has been very challenging to analyze on an atomic level.

Publishing their findings in Science, researchers used a new, highly advanced imaging technique called single-particle cryo-electron microscopy (cryo-EM) to study the HIV intasome. They discovered differences between the core structural components of this intasome and that of PFV and found that HIV intasomes are more intricate and complex than those of other retroviruses. This complexity likely indicates that HIV is a more evolved retrovirus and helps explain why it operates in ways that other retroviruses are not able, such as the ability to enter the nucleus of a cell without having to wait until it divides.

To read the study abstract, click here.

To read a press release about the study, click here.