Human adenoviruses have been the subject of intensive investigation since their discovery in the early 1950s: they have served as model pathogens, as probes for studying cellular processes and, more recently, as efficient gene-delivery vehicles for experimental gene therapy. As a result, a detailed insight into many aspects of adenovirus biology is now available. The capsid proteins and in particular the hexon, penton-base and fibre proteins (the so-called major capsid proteins) have been studied extensively and their structure and function in the virus capsid are now well-defined. On the other hand, the minor proteins in the viral capsid, i.e. proteins IIIa, VI, VIII and IX, have received much less attention. Only the last few years have witnessed a sharp increase in the number of studies on their structure and function. Here, a review of the minor capsid proteins is provided, with a focus on new insights into their position and role in the capsid and the opportunities that they provide for improving human adenovirus-derived gene-delivery vectors.
The 14.4-kDa hexon-associated protein IX (pIX) acts as a cement in the capsids of primate adenoviruses and confers a thermostable phenotype. Here we show that deletion of amino acids 100 to 114 of adenovirus type 5 pIX, which eliminates the conserved coiled-coil domain, impairs its capacity to self-associate. However, pIX⌬100-114 is efficiently incorporated into the viral capsid, and the resulting virions are thermostable. Deletion of the central alanine-rich domain, as in pIX⌬60-72, does not impair self-association, incorporation into the capsid, or the thermostable phenotype. These data demonstrate, first, that the self-association of pIX is dispensable for its incorporation into the capsid and generation of the thermostability phenotype and, second, that the increased thermostability results from pIX monomers binding to different hexon capsomers rather than capsid stabilization by pIX multimers.
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