Using a new combination of imaging techniques, researchers have discovered a possible method to break down the protective protein coat surrounding the HIV genome and render the virus less infectious.
Structural biologists at the University of Pittsburgh School of Medicine have studied the conical-shaped capsid—or protein coat—of the HIV genome in greater detail than ever has ever been done before. Previous studies have used a combination of x-ray crystallography and image reconstruction techniques to study the protein coat. In the new study, researchers used cryo-electron microscopy (cryoEM) and high-resolution nuclear magnetic resonance (NMR) microscopy to determine the capsid’s functional importance.
The researchers also identified seams along which experimental mutagenesis can control the assembly and the disassembly of the protein coat.
When the seam at the junction between the capsid protein C-terminal domain dimers is modified by mutagenesis, it presents alterations in tubular assembly, according to the paper.
“Our lab experiments show that if we replace a few of the pivotal stitches in the seam by mutation, the resulting viruses are less infectious or even non-infectious,” co-author Angela Gronenborn said in a press release. Gronenborg is chair of the department of structural biology at the University of Pittsburgh School of Medicine and co-director of the University of Pittsburgh Center for HIV Protein Interactions. “The capsid, and therefore the virus, can no longer function properly.”
Co-author Peijun Zhang, assistant professor in the department of structural biology at the University of Pittsburgh School of Medicine, said that this new understanding of the structure and functions of the capsid “will allow scientists to rationally design therapeutic compounds that interfere with assembly of the protein and affect its function.”
The paper, “Structural convergence between cryoEM and NMR reveals inter-subunit interactions critical for HIV-1 capsid function,” was published online Nov. 13 in Cell. The work was a result of a collaboration between the University of Pittsburgh School of Medicine and researchers in the department of microbiology and immunology at the Vanderbilt University School of Medicine in Nashville, TN.