The effect of hypoxia on the uptake, replication and lytic potential of group B adenovirus type 3 (Ad3) and type 11p (Ad11p).
Replicating, tumor selective viruses are being tested as potential treatments for human cancers. Hypoxia is a pathophysiological cancer condition that alters the lytic potential of the replication-competent adenovirus serotype 5 (Ad5) virus by a mechanism independent of receptor levels or internalization rates. We extend these initial studies to examine the potential effects of hypoxia on the group B adenoviruses (Ads), adenovirus type 3 (Ad3) (group B1) and adenovirus type 11p (Ad11p) (group B2). Receptor expression (CD46) is not altered by hypoxia. However, the lytic potential is compromised in a cell-dependent fashion. Consequently, our study suggests that group B replicating Ad-based treatments, like the group C Ad-5-based viruses, will need to be modified in order to effectively treat hypoxic components of human tumors.
Shen
B H
BH
Gene Therapy Research Department, Berlex Biosciences, Richmond, CA 94806, USA.
Bauzon
M
M
Hermiston
T W
TW
D000257:Adenoviridae Infections / Q000821:virology*; D000260:Adenoviruses, Human / Q000235:genetics / Q000502:physiology*; D003588:Cytopathogenic Effect, Viral; D005434:Flow Cytometry; D015316:Genetic Therapy / Q000379:methods*; D005838:Genotype; D019337:Hematologic Neoplasms / Q000378:metabolism / Q000628:therapy* / Q000821:virology; D006801:Humans; D000860:Hypoxia / Q000821:virology*; D051916:Membrane Cofactor Protein / Q000378:metabolism; D050130:Oncolytic Virotherapy / Q000379:methods*; D014779:Virus Replication
D051916:Membrane Cofactor Protein