Double-stranded RNA confers both preventive and therapeutic effects against Penaeus stylirostris densovirus (PstDNV) in Litopenaeus vannamei

Nucleic-acid based antivirals: Augmenting RNA interference to ‘vaccinate’ Litopenaeus vannamei

“…We have summarized this work on L. vannamei in Table 1, which delineates the target, dose of RNAi trigger, and resulting survival rate (if available) for each study. The data in Table 1 reveal no particular predictability in target choice efficacy based on virus gene category (structural or non-structural), and do not necessarily support the idea put forth that non-structural targets are good targets for RNAi trigger development because these tend to have to less abundant transcript levels relative to structural genes (Ho et al, 2011). Several RNAi triggers based on structural protein coding regions in the WSSV genome appear to provide strong protection from disease.…”

“…There is ample evidence that specific RNAi triggers mitigate viral disease in shrimp caused by, for example, WSSV (Robalino et al, 2005;Xu et al, 2007), YHV (Tirasophon et al, 2005;Yodmuang et al, 2006;Tirasophon et al, 2007), PstDNV (formerly Infectious hypodermal and hematopoietic necrosis virus (IHHNV) (Ho et al, 2011), TSV (Robalino et al, 2005) and IMNV (Loy et al, 2012). Given the gravity of the economic impact of endemic viral disease, and in the interest of preparedness for emerging disease outbreaks, strategic development of new RNAi triggers as antiviral molecules is of great interest.…”

“…For example, a dsRNA directed to a nonstructural protease from YHV provided 100% protection from disease in P. monodon at a dose of 25 lg/5 g animal (Yodmuang et al, 2006), and a dsRNA directed to ORF1/2 in PstDNV, which encodes non-structural protein NS1, provided complete virus clearance in L. vannamei as measured by PCR (Ho et al, 2011). In the case of WSSV and TSV, a small degree of disease protection was provided by injecting animals with a non-specific (to both host and virus) dsRNA sequence (see also Table 1).…”

Sequence-optimized and targeted double-stranded RNA as a therapeutic antiviral treatment against infectious myonecrosis virus in Litopenaeus vannamei

“…Previous studies of the potential therapeutic effect of dsRNA on YHV or PstDNV disease revealed such an effect only with higher doses and shorter intervals between exposure and treatment. For example, a 25.0 µg dose of dsRNA provided protection 3 or 12 h after YHV infection (Tirasophon et al 2007), and a 5.0 to 12.5 µg dose of dsRNA was protective 24 h post-PstDNV infection (Ho et al 2011). No experimental studies have examined the replication dynamics of IMNV in shrimp, but the data presented here suggest that a large amount of virus replication occurs between 48 and 72 h post-infection, after which time the survival-enhancing effect of dsRNA treatment is reduced.…”

“…RNA interference (RNAi) is one possible and promising method to mitigate viral disease in shrimp (Robalino et al 2005, Krishnan et al 2009, Shekhar & Lu 2009, Hirono et al 2011. RNAi has been used to prevent shrimp disease caused by white spot syndrome virus (WSSV) (Robalino et al 2005, Xu et al 2007, yellowhead virus (YHV) (Tirasophon et al 2005, Yodmuang et al 2006, Taura syndrome virus (TSV) (Robalino et al 2004), Penaeus stylirostris densovirus (PstDNV) (formerly called infectious hypodermal and hematopoietic necrosis virus, IHHNV) (Ho et al 2011), and IMNV . In addition to administration prior to viral exposure, the potential for a therapeutic effect using RNAi has been tested against many different RNA viruses and DNA viruses of animals and humans, several of which are being evaluated in Phase 1 and 2 human clinical trials as antiviral therapeutics (Haasnoot et al 2007).…”