Regulation of Human Adenovirus Replication by RNA Interference.
Adenoviruses cause a wide variety of human infectious diseases. Adenoviral conjunctivitis and epidemic keratoconjunctivitis are commonly associated with human species D adenoviruses. Currently, there is no sufficient or appropriate treatment to counteract these adenovirus infections. Thus, there is an urgent need for new etiology-directed therapies with selective activity against human adenoviruses. To address this problem, the adenoviral early genes E1A and E2B (viral DNA polymerase) seem to be promising targets. Here, we propose an effective approach to downregulate the replication of human species D adenoviruses by means of RNA interference. We generated E1A expressing model cell lines enabling fast evaluation of the RNA interference potential. Small interfering RNAs complementary to the E1A mRNA sequences of human species D adenoviruses mediate significant suppression of the E1A expression in model cells. Furthermore, we observed a strong downregulation of replication of human adenoviruses type D8 and D37 by small hairpin RNAs complementary to the E1A or E2B mRNA sequences in primary human limbal cells. We believe that our results will contribute to the development of efficient anti-adenoviral therapy.
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilova Str., 32, Moscow, 119991, Russia.
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Nikitenko
Heinrich Pette Institute - Leibniz Institute for Experimental Virology, Martinistrasse 52 D-20251, Hamburg, Germany.
T
T
Speiseder
Heinrich Pette Institute - Leibniz Institute for Experimental Virology, Martinistrasse 52 D-20251, Hamburg, Germany.
E
E
Lam
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilova Str., 32, Moscow, 119991, Russia.
P M
PM
Rubtsov
S.N. Fedorov Eye Microsurgery Complex of the Ministry of Health of the Russian Federation, Beskudnikovskiy Blvd., 59A, Moscow, 127486, Russia.
Kh D
KhD
Tonaeva
S.N. Fedorov Eye Microsurgery Complex of the Ministry of Health of the Russian Federation, Beskudnikovskiy Blvd., 59A, Moscow, 127486, Russia.
S A
SA
Borzenok
Heinrich Pette Institute - Leibniz Institute for Experimental Virology, Martinistrasse 52 D-20251, Hamburg, Germany.
T
T
Dobner
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilova Str., 32, Moscow, 119991, Russia.
V S
VS
Prassolov
RNA interference; human adenoviruses; lentiviral vectors; small hairpin RNAs; small interfering RNAs