title: Targeting species D adenoviruses replication to counteract the epidemic keratoconjunctivitis.
abstract: Human adenoviruses are non-enveloped DNA viruses causing various infections; their pathogenicity varies dependent on virus species and type. Although acute infections can sometimes take severe courses, they are rarely fatal in immune-competent individuals. Adenoviral conjunctivitis and epidemic keratoconjunctivitis are hyperacute and highly contagious infections of the eye caused by human adenovirus types within species D. Currently there is no causal treatment available to counteract these diseases effectively. The E2B region of the adenovirus genome encodes for the viral DNA polymerase, which is required for adenoviral DNA replication. Here we propose novel model systems to test this viral key factor, DNA polymerase, as a putative target for the development of efficient antiviral therapy based on RNA interference. Using our model cell lines we found that different small interfering RNAs mediate significant suppression (up to 90%) of expression levels of viral DNA polymerase upon transfection. Moreover, permanent expression of short hairpin RNA based on the most effective small interfering RNA led to a highly significant, more than tenfold reduction in replication for different human group D adenoviruses involved in ocular infections.
authors: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilova Street 32, 119991 Moscow, Russia.
authors: Natalia A
authors: NA
authors: Nikitenko
authors: Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Martinistrasse 52, D-20251 Hamburg, Germany.
authors: Thomas
authors: T
authors: Speiseder
authors: Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Martinistrasse 52, D-20251 Hamburg, Germany.
authors: Peter
authors: P
authors: Groitl
authors: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilova Street 32, 119991 Moscow, Russia.
authors: Pavel V
authors: PV
authors: Spirin
authors: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilova Street 32, 119991 Moscow, Russia.
authors: Maria M
authors: MM
authors: Prokofjeva
authors: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilova Street 32, 119991 Moscow, Russia.
authors: Timofey D
authors: TD
authors: Lebedev
authors: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilova Street 32, 119991 Moscow, Russia.
authors: Petr M
authors: PM
authors: Rubtsov
authors: Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Martinistrasse 52, D-20251 Hamburg, Germany.
authors: Elena
authors: E
authors: Lam
authors: Research Department Cell and Gene Therapy, Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany.
authors: Kristoffer
authors: K
authors: Riecken
authors: Research Department Cell and Gene Therapy, Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany.
authors: Boris
authors: B
authors: Fehse
authors: Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Martinistrasse 52, D-20251 Hamburg, Germany.
authors: Thomas
authors: T
authors: Dobner
authors: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilova Street 32, 119991 Moscow, Russia. Electronic address: prassolov45@mail.ru.
authors: Vladimir S
authors: VS
authors: Prassolov
mesh_terms: D000256:Adenoviridae / Q000502:physiology*; D000258:Adenovirus Infections, Human / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000818:Animals; D004259:DNA-Directed DNA Polymerase / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D007639:Keratoconjunctivitis, Infectious / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000821:virology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects* / Q000235:genetics
chemical_list: D034741:RNA, Small Interfering; D004259:DNA-Directed DNA Polymerase
keywords: Adenoviral infections; Human adenoviruses; Lentiviral vectors; RNA interference