Evidence for the role of His-142 of protein 1C in the acid-induced disassembly of foot-and-mouth disease virus capsids

• Published in: Journal of general virology Vol. 80; no. 8; pp. 1911 - 1918
• Main Authors: Ellard, F.M, Drew, J, Blakemore, W.E, Stuart, D.I, King, A.M.Q
• Format: Journal Article
• Language: English
• Published: England Soc General Microbiol 01.08.1999
• Subjects: Animals; Aphthovirus; Aphthovirus - physiology; Capsid - physiology; Capsid Proteins; Cell Line; coat proteins; Cricetinae; Foot-and-mouth disease virus; Histidine - physiology; Hydrogen-Ion Concentration; Mutagenesis, Site-Directed; Virus Assembly
• ISSN: 0022-1317; 1465-2099
• DOI: 10.1099/0022-1317-80-8-1911

Foot-and-mouth disease virus (FMDV) capsids are inherently labile under mildly acidic conditions, dissociating to pentamers at pH values in the region of 6.5, with the release of protein 1A and the viral RNA. This acid-induced disassembly is thought to be required for the entry of the virus genome into the host cell. Previous work has highlighted a histidine-alpha-helix charge-dipole interaction at the twofold axes of symmetry between pentamers and has suggested that this interaction plays a role in acid-induced disassembly. The validity of this theory has now been tested by converting the implicated residue, His-142 of protein 1C, to Arg, Phe and Asp. The effects of such changes were studied by using a previously described vaccinia virus expression system, in which synthesis and processing of FMDV capsid proteins results in the self-assembly of capsids. In agreement with the histidine-alpha-helix charge-dipole theory, assembly in the arginine mutant was found to be greatly reduced, while capsids of the aspartic acid mutant were considerably more stable under acidic conditions than the wild-type. Aberrant but acid-stable complexes were obtained in the phenylalanine mutant.