From the targets identified to date (Table 1, Figure 1) it is apparent that viral miRNAs play an important role in immune evasion by inhibiting immune surveillance and extending the life of the infected host cell. Table 1 Immunomodulatory viral miRNAs.
More studies from recent reports indicate miR-K12-5, miR-K12-9 and miR-K12-10 repression of Bcl-2-associated transcription factor 1, an apoptosis-inducing factor (238), miR-K12-3 reduction of LRRC8D (leucine rich repeat containing 8 family, member D), a leucin-rich type III transmembrane protein involved in proliferation and activation of lymphocytes, NHP2L1 (non-histone chromosome protein 2-like 1) (239), and a transcription factor NFIB (240), miR-K12-1 inhibition of p21 (241) and NFkappaB inhibitor IkappaBalpha (242), miR-K12-4-3p suppression of GEMIN8 (239), miR-K12-10a reduction of TWEAKR (243), miR-K12-1, -6, and -11 decrease of MAF (musculoaponeurotic fibrosarcoma oncogene homolog) (244), K12-4-5p targeting retinoblastoma (Rb)-like protein 2 (Rbl2) and miR-K12-5 and -9*suppressing ORF50 mRNA (245,246).
Here, we report that cellular mRNAs encoding the cellular cyclin-dependent kinase inhibitor p21, a key inducer of cell cycle arrest, are direct targets for KSHV miR-K1. Ectopically expressed KSHV miR-K1 specifically inhibited the expression of endogenous p21 in KSHV-negative cells and strongly attenuated the cell cycle arrest that normally occurs upon p53 activation.
