Enhanced inhibition of Avian leukosis virus subgroup J replication by multi-target miRNAs

Abstract

BackgroundAvian leukosis virus (ALV) is a major infectious disease that impacts the poultry industry worldwide. Despite intensive efforts, no effective vaccine has been developed against ALV because of mutations that lead to resistant forms. Therefore, there is a dire need to develop antiviral agents for the treatment of ALV infections and RNA interference (RNAi) is considered an effective antiviral strategy.ResultsIn this study, the avian leukosis virus subgroup J (ALV-J) proviral genome, including the gag genes, were treated as targets for RNAi. Four pairs of miRNA sequences were designed and synthesized that targeted different regions of the gag gene. The screened target (i.e., the gag genes) was shown to effectively suppress the replication of ALV-J by 19.0-77.3%. To avoid the generation of escape variants during virus infection, expression vectors of multi-target miRNAs were constructed using the multi-target serial strategy (against different regions of the gag, pol, and env genes). Multi-target miRNAs were shown to play a synergistic role in the inhibition of ALV-J replication, with an inhibition efficiency of viral replication ranging from 85.0-91.2%.ConclusionThe strategy of multi-target miRNAs might be an effective method for inhibiting ALV replication and the acquisition of resistant mutations.

Newly detected mutations in the Meq oncogene and molecular pathotyping of very virulent Marek’s disease herpesvirus in Tunisia

“…On the other hand, the presence of the amino acids R 119 , Q 153 and A 176 , has been shown to be a common feature of the American vv isolates 549 (AY362714) and 595 (AY362715) and the American vv + isolates N, L, X, 584A, and 684A (AY362725), in contrast to a report by Tian et al . [ 4 ], who suggested that these mutations are unique in vv + strains. However, the Tunisian isolates share R 119 , and P 176 as well as P 153 .…”

“…DNA extracted from the tissues was amplified using primer pairs described by Tian et al . [ 4 ], Becker et al . [ 25 ], and Hassanin et al [ 26 ] .…”

A Recombinant Avian Leukosis Virus Subgroup J for Directly Monitoring Viral Infection and the Selection of Neutralizing Antibodies

“…Gag, pol and LTR coding regions of RCAS(A)GFP are not completely identical within HPRS-103. Furthermore, gag, pol and LTR regions are all involved in the replication of ALV within avian cells [14] , [15] . Hence, the titer of RCAS(J)GFP and rHPRS-103EGFP are different although they both are ALV-J expressing EGFP molecular clones.…”

Enhanced Antiviral Ability by a Combination of Zidovudine and Short Hairpin RNA Targeting Avian Leukosis Virus

“…At present, there are several reports on the application of RNAi to inhibit ALV ( Chen et al, 2007 ; Meng et al, 2011 ; Wei et al, 2015 ). Similarly, in this study, shRNA expression plasmids were used to inhibit the replication of ALV-J.…”