Role of RNA helicases in HIV-1 replication

Jeang, Kuan-Teh; Yedavalli, Venkat

Given that the HIV-1/AIDS disease burden has reached pandemic global proportions, new antiviral strategies that target molecularly delineated mechanisms used by this virus are urgently needed (72) . Is there a possibility that host cell helicases can be therapeutic targets for anti-HIV-1 chemotherapy? Implicit within this question is the concept that one could attack a host cell protein in order to treat an infecting pathogen. Although targeting a cellular protein involved in a viral pathway risks obvious cytotoxicity, this approach avoids the inherent problem posed by rapid HIV-1 mutation to all currently utilized chemotherapeutics targeted to virus-encoded proteins. We note that inhibition of cell-encoded enzymes in medical therapy is not an unprecedented strategy. Suppression of angiotensin-converting enzyme (ACE) is widely used to treat hypertension, congestive heart failure, myocardial infarction, endothelial dysfunction and renal disease (73) . Elsewhere, aromatase inhibitors have been used to treat hormone-dependent breast cancer (74) , and inhibitors of cellular secretory proteases are contemplated for Alzheimer's disease (75) . We recently inhibited the cellular polyprotein convertase, furin, at minimal toxicity to the cell in order to block HIV-1 replication (76). Thus, a priori exclusion of cellular helicase as an antiviral target is not warranted.