We propose to study the interaction of type C strains of adenovirus with proliferative and differentiation programs of the host cell. During its life cycle in natural hosts, adenovirus normally infects non-dividing cells. We propose to investigate the ability of the virus to induce in host cells proliferative functions which the cell normally expresses during active growth and which, according to our hypothesis, the virus diverts for the benefit of the viral life cycle. In so stimulating the infected cell, the virus may establish in its host a state normally occuring in rapidly dividing cells, or in cells with extended proliferative capacity, such as stem cells or progenitor cells. We shall also investigate whether the virus represses specialized differentiated cell functions which are expressed in terminally differentiated cells with limited proliferative capacity. The primary viral regulators of cellular proliferative functions are proposed to be the E1a proteins, which we suggest perform not only their well recognized role of regulating the transcription of viral early genes, but also act on cellular genes which are regulators of cell proliferation and differentiation.
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