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A team led by scientists at the Scripps Research Institute and the University of Amsterdam has achieved an important goal in virology: mapping key proteins that attach to the surface of the hepatitis C virus (HCV) and enable it to enter host cells at high resolution.

 

The findings, published recently in Science, detail the key vulnerable sites of the virus, which can now be effectively targeted by vaccines.

 

Dr. Gabriel Lander, a professor in the Department of Integrated Structural and Computational Biology at the Scripps Research Institute and senior co-author of the study, said: "This long-standing and interesting structural information on HCV incorporates a large number of previous observations into the structural context, paving the way for rational vaccine design against this incredible goal."

 

The study is the product of years of collaboration and includes the Ward laboratory, Dr. Gabriel Lander’s laboratory (also a professor in the Department of Integrated Structure and Computational Biology at the Scripps Research Institute); Dr. Rogier Sanders' laboratory at the University of Amsterdam; and Max Crispin's laboratory at the University of Southampton.

 

It is estimated that about 60 million people worldwide, including about 2 million Americans, have chronic hepatitis C virus infection. This virus infects liver cells and usually forms a "silent" infection over decades until liver damage is severe enough to cause symptoms. It is a major cause of chronic liver disease, liver transplantation, and primary liver cancer.

 

The origin of the virus is uncertain, but it is thought to have emerged at least several hundred years ago and eventually spread worldwide through blood transfusion in the second half of the 20th century. Although the virus was essentially eliminated from blood banks after its first discovery in 1989, it continues to spread mainly through needle sharing among intravenous drug users in developed countries and the use of unsterilized medical devices in developing countries. Major hepatitis C antivirals are effective, but too expensive for mass treatment.

 

An effective vaccine may ultimately eliminate HCV as a public health burden. However, no such vaccine has been developed to date, mainly because it is very difficult to study the envelope protein complex of hepatitis C virus, which consists of two viral proteins E1 and E2.

 

"The E1E2 composite structure is very fragile—it is like a bag of wet spaghetti and always changing shape—which is why imaging at high resolution is very challenging," said co-first author Dr. Lisa Eshun-Wilson.

 

In this study, the researchers found that they could use a combination of three broadly neutralizing anti-HCV antibodies to stabilize the natural conformation of the E1E2 complex. Broadly neutralizing antibodies are those that protect themselves from a variety of viral strains by binding to relatively invariable sites on the virus in a manner that interrupts the viral life cycle.

 

The researchers used cryo-electron microscopy to image antibody stable protein complexes. With the help of advanced image analysis software, researchers were able to generate E1E2 structural maps at near atomic-scale resolution, which are unprecedented in clarity and breadth.

 

Details include most E1 and E2 protein structures, including critical E1/E2 interfaces, and three antibody binding sites. Structural data also revealed "glycan" molecules associated with sugars on top of E1E2. Viruses usually use glycans to protect themselves from the immune system of infected hosts, but in this case, structural data show that glycans of hepatitis C virus clearly have another key role: helping to fix fragile E1E2 complexes together. Understanding these details of E1E2 will help researchers rationally design a vaccine that can robustly stimulate these antibodies to prevent HCV infection.

Creative Biostructure, a forward-looking research company as well as custom service provider in the field of microscopy technology, recently launched an iEM platform to provide customers high-resolution imaging of the surface of mammalian cells and tissues.

 

In biological research and pathology, ultrastructural analysis of cells and tissues is crucial. An effective tool for examining the morphology of cells and tissues is electron microscopy (EM). EM is an imaging method that produces high-resolution images of specimens by illuminating them with a beam of accelerated electrons. These images, which were obtained using EM and AFM, offer a strong foundation for numerous studies and help to achieve the desired outcomes.

 

With tedious work of the scientist team at Creative Biostructure, the company introduced the iEM Platform, an integrated platform for electron microscopy (EM) and other microscopy technologies, including confocal laser scanning microscopy (CLSM), atomic force microscopy (AFM), and related hardware and software.

 

Service offerings at Creative Biostructure mainly include:

 

Brain cell imaging

Neuron imaging, Glial cell imaging

Adipocyte imaging

Imaging of various adipocytes within their native microenvironment, including white adipocytes, beige adipocytes, and brown adipocytes

Stem cell imaging

Characterization of purity and cell location, cellular function, and the differentiation state of stem cells

Bone tissue imaging

Characterization of exact bone disease phenotypes, investigation of the interaction between bone and implant devices, etc.

Sperm imaging

Evaluate sperm morphology, Sperm characterization for basic research, and Identify morphological sperm defects

Muscle tissue imaging

Routine EM for muscle tissue research, Cryo-ET for muscle tissue research

Blood cell imaging

Red blood cell imaging, White blood cell imaging, Platelet imaging

 

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“We are able to offer important details on the structural underpinnings of cell and tissue function as well as the interaction between the cells and their environment thanks to specialized equipment and skilled technical staff.” Said Joanna, the chief marketing staff Creative Biostructure.

 

To know more detailed information about iEM platform supported cell & tissue morphology service provided by Creative Biostructure, please visit https://iem.creative-biostructure.com/cell-&-tissue-morphology.html.