Retrovirus capsid assembly
A retrovirus has a lipoprotein envelope lined with a layer of matrix protein (MA), surrounding a nucleoprotein core. In the core, the diploid RNA genome in complex with nucleocapsid protein (NC) and the replication enzymes is enclosed within the capsid – a shell of CA protein. MA, CA and NC are derived from a common precursor, the Gag polyprotein, which assembles into a thick-walled spherical shell in the immature virus. After it buds off from the host cell, the viral protease is activated, releasing CA subunits that assemble into capsids. Capsids of a given retrovirus vary in structure, and the predominant types vary among retroviruses; for instance, those of HIV are conical, those of Rous sarcoma virus (RSV) are irregular polyhedra and those of murine leukemia virus are round. Some virions contain more than one capsid, and nested (multilayer) capsids are also observed.
For a retrovirus such as HIV to be infectious, a properly formed capsid is needed; however, unusually among viruses, retrovirus capsids are highly variable in structure. According to the fullerene conjecture, they are composed of hexamers and pentamers of capsid protein (CA), with the shape of a capsid varying according to how the twelve pentamers are distributed and its size depending on the number of hexamers. Hexamers have been studied in planar and tubular arrays, but the predicted pentamers have not been observed. Here we report cryo-electron microscopic analyses of two in-vitro-assembled capsids of Rous sarcoma virus. Both are icosahedrally symmetric: one is composed of 12 pentamers, and the other of 12 pentamers and 20 hexamers. Fitting of atomic models of the two CA domains into the reconstructions shows three distinct inter-subunit interactions. These observations substantiate the fullerene conjecture, show how pentamers are accommodated at vertices, support the inference that nucleation is a crucial morphologic determinant, and imply that electrostatic interactions govern the differential assembly of pentamers and hexamers.
Visualization of a missing link in retrovirus capsid assembly. Nature 457: 694-698 (5 February 2009)
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Tags: Biology, HIV/AIDS, Microbiology, Science, Virology
