The present invention relates to compositions comprising a novel recombinant virus which replicates selectively in cells or tissues that are hypoxic or have an activated HIF pathway. The novel compositions of the invention comprise a recombinant virus genetically engineered to have a hypoxia/HIF-responsive element, or a multiplicity of such elements, operably linked to a promoter which is in turn operably linked to a nucleic acid(s) encoding a peptide(s) which regulates or modulates replication of the virus and/or encode a therapeutic molecule. The invention also includes constructs useful for screening of agents which interact with proteins or genes in the hypoxia-inducible pathway or are jointly translated under hypoxia and animal models useful for monitoring a variety of hypoxic conditions in a non-invasive manner.