Two days ago, on October 17th , a paper published on the Science journal first revealed the architecture of African Swine Fever (ASF) virus!
This is such an exciting work and has important implications for viral assembly & potentially, for vaccine development.
It was a collaborative work by Chinese Academy of Sciences, Chinese Academy of Agricultural Sciences, University of Chinese Academy of sciences, Shanghai Tech University, Tsinghua University, and Nankai University.
I don't think there is a need for much background introduction...With this devastating and highly contagious disease of ASF affecting so many countries now and posing serious challenges to the global protein industry, there is an emergent need to understand how this virus (ASFV) works to figure out ways to counteract it (e.g. develop effective vaccine).
The first step, of course, is to understand its structure.
What was done?
Using cryo-electron microscopy (EM) observation and an optimized image reconstruction strategy, the researchers solved the ASFV architecture and the capsid structure.
It was reported that the researchers have worked on this project day and night for 4 months and collected > 100 TB data to solve the 3D structure of the virus.
Also, for a virus at this size, previous observation can reach a resolution at 10 Å (angstroms) at best, while for this study, they were able to obtain an 8.8 Å resolution for the ASFV particle and 4.1 Å for the capsid, which is a huge advancement!
What was found?
- ASF Virus Architecture
The researcher revealed the 5-layer structure of the ASF virus:
- Layer 1: A genome containing nucleoid
- Layer 2: A thick protein layer (aka. the core shell)
- Layer 3: An inner lipid envelope
- Layer 4: An icosahedral protein capsid
- Layer 5: An external envelop
The diameter of the ASF virus is 260 to 300 nm.
The capsid (layer 4, which is the protein shell of a virus) is built "from 17, 280 proteins, including one major (p72) and four minor capsid proteins (M1249L, p17, p49 and H240R), organized into pentasymmetrons and trisymmetrons".
(A). Cross-section of the 5-layer ASFV virion structure. (B). ASFV capsid and core shell. (C). ASFV capsid in its trisymmetron and pentasymmetry organization. (D). Diagrammatic organization of the minor capsid proteins and capsomers viewed from inside capsid.
- Proposed assembly pathway of the ASFV capsid
Below is how the researchers propose that the ASFV capsid (the 4th layer) assembles --- Basically, on top of the core shell (2nd layer), the viral inner membrane precursors start to appear and exhibit various inner membrane proteins, then,
➜ The pento complexes associate with the inner membrane recruit p72 capsomers (purple), which initiates the assembly (A)
➜ The "zipper" structure (which is the boundaries of the 2 neighboring trisymmetrons, as shown in blue below) is assembled with mediated by skeleton protein M1249L and p72 capsomers (B)
➜ The polyhedral cage is constructed by 12 pentasymmetrons (the purple ones) and 30 zippers (C)
➜ As a final step, the p72 capsomers (the yellow ones) fill in the trisymmetrons to complete the capsid assembly (D)
As we can see in the figure below (B), The M1249L proteins "run along each edge of trisymmetrons bridging two neighboring pentasymmtrons and form extensive intermolecular networks with other capsid proteins, driving the formation of the capsid framework".
All of the capsid proteins "form a complicated network..., stabilizing the capsid by holding adjacent capsomers together", that is probably why the ASF is so stable.
- Potential epitopes for ASF vaccine?
The researchers found that the p72 capsomer contains 4 exposed regions (ERs), as shown below in (C) - ER 1, 2, 3, and 4. which may "define the neutralizing epitopes and could be used to guide ASF vaccine design".
(An epitope is the part of an antigen that is recognized by the immune system, specifically by antibodies, B cells, or T cells)
Take home message
It is amazing that we now have a better idea of how the ASF virus is structured! The virus architecture is indeed complex and stable, and much more work is needed to better understand it, but at least we have some clues and leads for potential vaccine development!
As the authors stated, "The ASFV architecture at near-atomic resolution reported here allows us to take the first steps toward understanding what drives the assembly of the capsid and the basis for its stability...(and) will impact the development of new strategies for vaccine intervention against ASFV infections."
Full article access👇
Nan Wang, Dongming Zhao, Jialing Wang, Yangling Zhang, Ming Wang, Yan Gao, Fang Li, Jingfei Wang, Zhigao Bu, Zihe Rao, Xiangxi Wang. 2019. Architecture of African swine fever virus and implicatiosn for viral assembly. Science. DOI: 10.1126
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