ADENOVIRUS TYPE-5 AND TYPE-7 CAPSID CHIMERA - FIBER REPLACEMENT ALTERS RECEPTOR TROPISM WITHOUT AFFECTING PRIMARY IMMUNE NEUTRALIZATION EPITOPES

The efficient uptake of adenovirus into a target cell is a function of adenovirus capsid proteins and their interaction with the host cell. The capsid protein fiber mediates high-affinity attachment of adenovir us to the target cell. Although the cellular receptor(s) for adenoviru s is unknown, evidence indicates that a single receptor does not funct ion as the attachment site for each of the 49 different serotypes of a denovirus. Sequence variation of the fiber ligand, particularly in the C-terminal knob domain, is associated with serotype-specific binding specificity. Additionally, this domain of fiber functions as a major s erotype determinant. Fiber involvement in cell targeting and its funct ion as a target of the host immune response make the fiber gene an att ractive target for manipulation, both from the perspective of adenovir us biology and from the perspective of using adenovirus vectors for ge ne transfer experiments. We have constructed a defective chimeric aden ovirus type 5 (Ad5) reporter virus by replacing the Ad5 fiber gene wit h the fiber gene from Ad7A. Using the chloramphenicol acetyltransferas e reporter gene, we have characterized this virus with respect to infe ctivity both in vitro and in vivo. We have also characterized the role of antifiber antibody in the host neutralizing immune response to ade novirus infection. Our studies demonstrate that exchange of fiber is a strategy that will be useful in characterizing receptor tropism for d ifferent serotypes of adenovirus. Additionally, the neutralizing immun e response to Ad5 and Ad7 does not differentiate between two viruses t hat differ only in their fiber proteins. Therefore, following a primar y adenovirus inoculation, antibodies generated against fiber do not co nstitute a significant fraction of the neutralizing antibody populatio n.