How a virus packages its genetic material
Simulations could help design nanocontainers used in drug delivery
Date:
March 9, 2022
Source:
University of California - Riverside
Summary:
Physics and astronomy professors have developed a theory and
performed a series of simulations that may help explain how a
virus finds its native genome and how capsids form around it and
not around other RNAs in the cell.
FULL STORY ==========================================================================
Each simple RNA virus has a genome, its "native RNA." This genome dictates
how the virus replicates in cells to eventually cause disease. The genome
also has the code for making a capsid, the protein shell of a virus that encapsulates the genome and protects it like a nanocontainer.
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A team led by Roya Zandi, a professor of physics and astronomy at
the University of California, Riverside, has developed a theory and
performed a series of simulations that may help explain how a virus
finds its native genome and how capsids form around it and not around
other RNAs in the cell.
"A better understanding of how capsids form is of vital importance
to material scientists and a crucial step in the design of engineered nano-shells that could serve as vehicles for delivering drugs to specific targets in the body," Zandi said.
The researchers' work, published in ACS Nano, shows that the interplay of
the mechanical properties of proteins, the size of the genome, and the
strength of the interaction between the genome and capsid proteins can significantly modify the symmetry, structure, and stability of the capsid.
When a virus enters a cell, the capsid breaks open to release the genome,
which then uses the cell's reproductive machinery to replicate. The
newly formed genomes begin to acquire their capsids, a process mainly
driven by the attractive electrostatic interaction between the positive
charges on capsid proteins and the negative charges on the genomes. But
how the virus selects and packages its native RNA inside the crowded environment of a host cell cytoplasm in the presence of many nonviral
RNA and other polymers has remained a mystery.
The simulations run by Zandi's team show that capsid proteins could, in
theory, pick any nonviral genome to encapsulate. But the viral genome,
she said, is best suited for capsid proteins to form a shell around due
to an interplay of energies at the molecular level.
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"The stress distribution of the capsid proteins is lower when the
capsids encapsulate their own genome, the one for which they were coded,"
Zandi said.
"The energy of the whole system is lower. While smaller nonviral RNAs
are available in the cell in plenty, the capsid proteins are inclined
toward forming a shell around a viral RNA because the resulting soccer ball-like shell has a lower stress distribution." Zandi said the work
lays out a systematic comparison of theory and experiments, which will
allow a better understanding of the role of RNA in the capsid assembly
pathway, stability, and structure.
"A deeper understanding of the role of the genome in virus assembly
mechanisms could lead to design principles for alternative antivirals,"
she said.
The new work is an early step in understanding viral assembly. The
process is not well understood because viruses measure in nanometers
and the assembly occurs in milliseconds.
"Theoretical work and simulations are necessary to understand how a
virus grows," Zandi said.
Zandi was joined in the research by graduate student Sanaz Panahandeh at
UCR; Siyu Li at Songshan Lake Materials Laboratory in China; and Bogdan
Dragnea at Indiana University, Bloomington. Li is a former graduate
student at UCR.
The research was funded by the National Science Foundation.
========================================================================== Story Source: Materials provided by
University_of_California_-_Riverside. Original written by Iqbal
Pittalwala. Note: Content may be edited for style and length.
========================================================================== Journal Reference:
1. Sanaz Panahandeh, Siyu Li, Bogdan Dragnea, Roya Zandi. Virus
Assembly
Pathways Inside a Host Cell. ACS Nano, 2022; 16 (1): 317 DOI:
10.1021/ acsnano.1c06335 ==========================================================================
Link to news story:
https://www.sciencedaily.com/releases/2022/03/220309165541.htm
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