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

Umesh Katpally, Thomas Smith

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Human rhinovirus 14 (HRV14) is a member of the rhinovirus genus, which belongs to the picornavirus family, which includes clinically and economically important members, such as poliovirus, foot-and-mouth disease virus, and endomyocarditis virus. 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 matrix-assisted laser desorption ionization analyses indicate that filling the drug-binding pocket with bulky side chains is not deleterious to the viral life cycle and lends some stabilization to the capsid. In contrast, studies with 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 "breathe" 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 the capsid dynamics, which is, in turn, necessary for infection.

Original languageEnglish (US)
Pages (from-to)6307-6315
Number of pages9
JournalJournal of Virology
Volume81
Issue number12
DOIs
StatePublished - Jun 2007
Externally publishedYes

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Human rhinovirus
Rhinovirus
Life Cycle Stages
life cycle (organisms)
capsid
Capsid
drugs
Pharmaceutical Preparations
Picornaviridae
cells
mutation
Foot-and-Mouth Disease Virus
Enterovirus C
Enterovirus
Mutation
Poliovirus
Foot-and-mouth disease virus
canyons
Virus Diseases
desorption

ASJC Scopus subject areas

  • Immunology

Cite this

Pocket factors are unlikely to play a major role in the life cycle of human rhinovirus. / Katpally, Umesh; Smith, Thomas.

In: Journal of Virology, Vol. 81, No. 12, 06.2007, p. 6307-6315.

Research output: Contribution to journalArticle

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