Abstract: Applicants have used microarrays, gene expression profiling, and gene silencing methods to identify and provide a plurality of ‘validated’ virus-induced cellular gene sequences (e.g., HMG20B, HRH1, NP and c-YES (src family kinases)) and pathways useful as therapeutic targets for modulation of viral-mediated cellular effects. Particular embodiments provide therapeutic compositions, and methods for modulation of viral infection, replication, maturation, progression, or other virally-related conditions or diseases, comprising inhibition of virally-induced gene sequences and gene products. Additional embodiments provide screening assays for compounds useful to modulate viral infection, replication, maturation or progression, or viral-related conditions or diseases. Further embodiments provide diagnostic and/or prognostic assays for viral infection, replication, maturation or progression. Preferably, the viruses all selected from the group consisting of retroviruses (e.g.