JVI Accepts, published online ahead of print on 11 April 2007

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J. Virol. doi:10.1128/JVI.00441-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Pocket factors unlikely play a major role in the life cycle of human rhinovirus

Umesh Katpally and Thomas J. Smith^*

Donald Danforth Plant Science Center, 975 North Warson Road, Saint Louis, MO 63132

^* To whom correspondence should be addressed. Email: tsmith{at}danforthcenter.org.

Human rhinovirus 14 is a member of the rhinovirus genus that belongs to the picornavirus family that includes clinically and economically important members such as poliovirus, foot and mouth disease virus (FMDV), and endomyocarditis virus (EMCV). Capsid stability plays an important role in the viral infection process, in that it needs to be stable enough to move from cell to cell and yet be able to release its genetic material upon the appropriate environmental cues from the host cell. It has been suggested that certain host cell molecules, ‘pocket factors’, bind to the WIN drug binding cavity beneath the canyon floor and provide transient stability to a number of the picornaviruses. To directly test this hypothesis, HRV14 was mutated in (V1188M, C1199W and V1188M/C1199W) and around (S1223G) the drug-binding pocket. Infectivity, limited proteolysis, and MALDI analyses indicate that filling the drug-binding pocket with bulky side chains is not deleterious to the viral life cycle and lend some stabilization to the capsid. In contrast, studies on the S1223G mutant suggest that this mutation at least partially overcomes WIN drug-mediated inhibition of cell attachment and capsid breathing. Finally, HRV16, which is inherently more stable than HRV14 in a number of respects, was found to ‘breath’ only at 37° C and did not tolerate stabilizing mutations in the drug-binding cavity. These results suggest that it is the drug binding cavity itself, and not the putative pocket factor, that is crucial for capsid dynamics that is, in turn, necessary for infection.

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