NOV 22, 2021 4:07 AM PST

Researchers Solve the Structure of the HIV Capsid, May Be a New Drug Target

WRITTEN BY: Carmen Leitch

Though treatments are available, there is no cure or vaccine from HIV, which impacts about 38 million people worldwide. It's difficult to target the RNA genome of the HIV virus in part because it mutates so frequently, and as a retrovirus, it can insert itself into the genome of a host cell. The capsid shell that surrounds the viral genome of HIV could offer another targeting strategy, and researchers have now deciphered its complex structure. With cutting edge tools, scientists built a near-atomic level model of the HIV capsid. The work has been reported in Science Advances.

From Sci Adv publication:  Structure of HIV capsid (L) Central slice of HIV virus-like particle with pore-forming toxin on the membrane (Middle) Atomic model of HIV capsid (R) Density map of HIV capsid components.

When HIV infects a host cell, the virus generates immature viral particles or virions with a dynamic molecule called Gag polyprotein, which can move through maturation and proteolytic stages, changing conformation from an immature sphere to a complete conical capsid. This capsid has a variety of important roles in HIV-1 replication; it can protect the viral genome from the host immune system, promote entry into a host cell's nucleus, control intracellular transport, and encourage reverse transcription to enter the host genome. These functions are influenced by various molecules and host cell proteins.

To elucidate the structure of proteins, one has to have a sample. That's a challenge for the HIV-1 capsid, which changes shape and is difficult to isolate intact in large quantities. Typical methods that are used to purify viral capsids aren't effective; they cause the HIV-1 capsid to dissociate. In this study, the researchers developed a new strategy that does not use detergent like the standard method.

 “Instead of detergent extraction, we punctuate the membrane of HIV virus-like particles with a pore-forming toxin, which avoids the trauma associated with lysis of the virions and isolation of the cores, but also makes the capsid accessible to external cell factors and small molecules," said lead study author Dr. Tao Ni of the University of Oxford.

The researchers were them able to use electron tomography and subtomogram averaging to analyze the interactions between the HIV-1 capsid and two molecules, Cyclophilin A (CypA), and cofactor IP6 (inositol hexakisphosphate). This work revealed the capsid's structure by itself, as well as its complex with CypA and IP6. There is a double IP6 binding site on the mature capsid, and the work revealed more about how these molecules help control the stability of the capsid.

“In collaboration with Professor Juan Perilla’s group in the University of Delaware, using information derived from electron tomography, we also built an atomistic model of the whole HIV capsid which could serve as a blueprint for the development of capsid-targeting antivirals. The perforation of the enveloped virus membrane also provides a novel approach to study host-virus interaction for other viral systems," said study leader Professor Peijun Zhang, Director of the eBIC at Diamond Light Source and a Professor of Structural Biology at the University of Oxford.

Sources: Diamond Light Source, Science Advances

About the Author
  • Experienced research scientist and technical expert with authorships on over 30 peer-reviewed publications, traveler to over 70 countries, published photographer and internationally-exhibited painter, volunteer trained in disaster-response, CPR and DV counseling.
You May Also Like
NOV 01, 2021
Cancer
Gut Microbiota Promotes Resistance to Prostate Cancer Therapy
NOV 01, 2021
Gut Microbiota Promotes Resistance to Prostate Cancer Therapy
  The American Cancer Society estimates that nearly 250,000 men in the United States will be diagnosed with prostat ...
NOV 09, 2021
Earth & The Environment
Ancient Egyptian Bees in Danger
NOV 09, 2021
Ancient Egyptian Bees in Danger
Honeybees have a long history in Egypt. Ancient Egyptians harvested honey from wild bees thousands of years ago, and bee ...
NOV 25, 2021
Microbiology
How Microbes Use Copper to Make an Antibiotic
NOV 25, 2021
How Microbes Use Copper to Make an Antibiotic
Copper is known to have antibacterial properties, and though it's an important chemical for many organisms, it can b ...
NOV 29, 2021
Microbiology
How the Hepatitis B Virus Promotes Liver Cancer Development
NOV 29, 2021
How the Hepatitis B Virus Promotes Liver Cancer Development
It's estimated that about 240 million people worldwide have an HBV infection. Hepatitis B infections are linked to t ...
DEC 21, 2021
Microbiology
Microbial Life Shows Mass Extinction Really Stinks
DEC 21, 2021
Microbial Life Shows Mass Extinction Really Stinks
There have been a few mass extinction events on our planet. One of them was apparently prolonged by microbes that were s ...
JAN 24, 2022
Microbiology
Potential Anti-Cancer Bacterium Found in Antarctic Sea Squirt
JAN 24, 2022
Potential Anti-Cancer Bacterium Found in Antarctic Sea Squirt
Some of our best medicine has come from nature, and scientists are always on the lookout for natural products that can b ...
Loading Comments...