Adenovirus infection of primary malignant lymphoid cells.
Adenovirus infection represents a cellular stress that induces host cell pro-apoptotic responses. To overcome this barrier to productive infection, viral polypeptides modulate a variety of host cell pathways. The interface of these early viral gene products with key cellular regulatory proteins has provided considerable information concerning basic cellular mechanisms operative in cell cycle regulation, transcriptional control and apoptosis. The overlap of these mechanisms with those impacted during oncogenesis provides the opportunity to use adenoviruses and adenovirus mutants to characterize the state of key regulatory pathways in specific malignant cells. For example, adenoviruses mediate cytotoxicity after infection of chronic lymphocytic leukemia (CLL) cells, mantle cell lymphoma (MCL) cells and multiple myeloma cell lines. Specific adenovirus mutants demonstrate enhanced cytotoxicity and, in many cases, apoptosis is not the primary mechanism of cell death. Analysis of these infections with respect to both the features of the primary malignant cell and the mechanisms of adenovirus-mediated cytotoxicity holds the prospect of providing novel insights into the status of key regulatory pathways in individual patient malignant cells. These studies also hold the prospect of supporting the development of specific attenuated adenoviruses as therapeutic agents with selective cytotoxicity for specific primary lymphoid malignancies.
Strair
Roger K
RK
The Cancer Institute of New Jersey, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, New Brunswick 08901, USA. strairrk@umdnj.edu
Sheay
Wendy
W
Goodell
Lauri
L
White
E
E
Rabson
Arnold B
AB
Medina
Daniel J
DJ
D000256:Adenoviridae / Q000235:genetics / Q000472:pathogenicity; D000257:Adenoviridae Infections / Q000473:pathology*; D016923:Cell Death; D006801:Humans; D007938:Leukemia / Q000473:pathology* / Q000821:virology; D008223:Lymphoma / Q000473:pathology* / Q000821:virology; D014407:Tumor Cells, Cultured