Targeting species D adenoviruses replication to counteract the epidemic keratoconjunctivitis

TY - JOUR

T1 - Targeting species D adenoviruses replication to counteract the epidemic keratoconjunctivitis

AU - Nikitenko, Natalia A

AU - Speiseder, Thomas

AU - Groitl, Peter

AU - Spirin, Pavel V

AU - Prokofjeva, Maria M

AU - Lebedev, Timofey D

AU - Rubtsov, Petr M

AU - Lam, Elena

AU - Riecken, Kristoffer

AU - Fehse, Boris

AU - Dobner, Thomas

AU - Prassolov, Vladimir S

N1 - Copyright © 2015 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

PY - 2015/3/19

Y1 - 2015/3/19

N2 - 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.

AB - 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.

U2 - 10.1016/j.biochi.2015.03.010

DO - 10.1016/j.biochi.2015.03.010

M3 - SCORING: Journal article

C2 - 25796214

VL - 113

SP - 10

EP - 16

JO - BIOCHIMIE

JF - BIOCHIMIE

SN - 0300-9084

ER -