Enhanced inhibition of porcine reproductive and respiratory syndrome virus replication by combination of morpholino oligomers

Han, Xue; Fan, Sumin; Patel, Dil V.; Zhang, Yan‐Jin

doi:10.1016/j.antiviral.2009.01.009

Cited by 19 publications

(14 citation statements)

References 26 publications

(46 reference statements)

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“…For the quantification of purified virus, PRRSV RNA was analyzed using quantitative real-time RT-PCR with primers designed against PRRSV ORF7 (Patel et al, 2008). A plasmid containing ORF7 sequence was used to generate a standard curve, and RNA copies in all samples were calculated based on it (Han et al, 2009). The transcript levels of cell-associated viral RNA were relatively quantified by the 2-ΔΔCT Method (Livak and Schmittgen, 2001).…”

Section: Quantitation Of Viral Rnamentioning

confidence: 99%

Lipid rafts both in cellular membrane and viral envelope are critical for PRRSV efficient infection

et al. 2015

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Porcine reproductive and respiratory syndrome virus (PRRSV) represents a significantly economical challenge to the swine industry worldwide. In this study, we investigated the importance of cellular and viral lipid rafts in PRRSV infection. First, we demonstrated that PRRSV glycoproteins, Gp3 and Gp4, were associated with lipid rafts during viral entry, and disruption of cellular lipid rafts inhibited PRRSV entry. We also showed the raft-location of CD163, which might contribute to the glycoproteins-raft association. Subsequently, raft disruption caused a significant reduction of viral RNA production. Moreover, Nsp9 was shown to be distributed in rafts, suggesting that rafts probably serve as a platform for PRRSV replication. Finally, we confirmed that disassembly of rafts on the virus envelope may affect the integrity of PRRSV particles and cause the leakage of viral proteins, which impaired PRRSV infectivity. These findings might provide insights on our understanding of the mechanism of PRRSV infection.

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Section: Quantitation Of Viral Rnamentioning

confidence: 99%

Lipid rafts both in cellular membrane and viral envelope are critical for PRRSV efficient infection

et al. 2015

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“…Therefore, successful supplementary strategies should include antiviral drugs and immune-modulation therapies (Benfield et al, 2002;Du et al, 2011;Han et al, 2009;Jiang et al, 2010;Karuppannan et al, 2012;Keirstead et al, 2008;Kreutz & Ackermann, 1996;Li et al, 2009;Opriessnig et al, 2011;Patel et al, 2008;te Velthuis et al, 2010;van der Meer et al, 2007;Wei et al, 2011;Yang et al, 2013;Zhuge et al, 2012). When evaluating the antiviral effect of tilmicosin against PRRSV, our data suggested that tilmicosin would be effective in reducing the PRRSV loads in vivo.…”

Section: Discussionmentioning

confidence: 99%

“…These data indicate that reducing the PRRSV load in the serum may prevent pigs from developing clinical signs after PRRSV infection. Several studies have attempted to identify effective anti-PRRSV treatments in vitro and in vivo (Benfield, Chase, Moore, Wagner, & Zeman, 2002;Du, Yoo, Paradis, & Scherba, 2011;Han, Fan, Patel, & Zhang, 2009;Jiang, Fang, Luo, Xiao, & Chen, 2010;Karuppannan, Wu, Qiang, Chu, & Kwang, 2012;Keirstead, Lee, Yoo, Brooks, & Hayes, 2008;Kreutz & Ackermann, 1996;Li et al, 2009;Opriessnig et al, 2011;Patel et al, 2008;te Velthuis et al, 2010;van der Meer et al, 2007;Wei et al, 2011;Yang et al, 2013;Zhuge et al, 2012). However, there are no effective commercial drugs available to prevent PRRSV infection in pigs in vivo.…”

Section: Introductionmentioning

confidence: 99%

Tilmicosin Reduces PRRSV Loads in Pigs in vivo

Lin¹,

Yang²,

Lin³

et al. 2015

JAS

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Porcine respiratory and reproductive syndrome virus (PRRSV) is an important pathogen having a significant economic impact on the swine industry worldwide. Tilmicosin is a new semi-synthetic macrolide antibiotic developed from tylosin B. Tilmicosin can enter pulmonary alveolar macrophages (PAMs) and inhibit the replication of PRRSV in PAMs in vitro. This study was conducted to evaluate the impact of tilmicosin in controlling the replication of PRRSV in vivo. Forty and 635 weaned piglets were randomly chosen from PRRSV-contaminated farrow-to-finish herds in Taiwan and China, respectively. The piglets were equally divided into two groups and housed in the same pen but separated into individual spaces. Tilmicosin (Tilmovet ® 20% premix, 400 mg/kg) was administered after weaning for 21 days (treated group). The untreated group of piglets did not receive tilmicosin. Blood samples were collected at 4, 6, 8, 10 and 12 weeks of age to detect of the PRRSV load. At 8 and 10 weeks of age, the tilmicosin-treated piglets had a significantly lower PRRSV load than the untreated piglets (P < 0.05) in Taiwan. At 6, 8, 10, and 12 weeks of age, the tilmicosin-treated piglets had a significantly lower PRRSV load than the untreated piglets (P < 0.05) in China. These data indicates that animals treated with tilmicosin exhibited not only reduced PRRSV loads but also improved average daily weight gain during the study period.

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“…Coronaviruses and arteriviruses are RNA viruses that share similar genomic structures. PMOs and arginine-rich peptide-conjugated PPMOs directed against the 5 0 UTR of equine arteritis virus (EAV) and against the 3 0 UTR of porcine reproductive and respiratory syndrome virus (PRRSV), respectively, have exhibited antiviral activity in in vitro translation assays and in cell culture (Han et al, 2009;Patel et al, 2008;van den Born et al, 2005;Zhang et al, 2006). Regions of the arterivirus genome which can be inhibited by PMOs have also shown to be target regions for inhibiting CoV.…”

Section: Use Of Morpholino Asos During Viral Infectionsmentioning

confidence: 99%

Advanced morpholino oligomers: A novel approach to antiviral therapy

2012

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Phosphorodiamidate morpholino oligomers (PMOs) are synthetic antisense oligonucleotide analogs that are designed to interfere with translational processes by forming base-pair duplexes with specific RNA sequences. Positively charged PMOs (PMOplus™) are effective for the postexposure protection of two fulminant viral diseases, Ebola and Marburg hemorrhagic fever in nonhuman primates, and this class of antisense agent may also have possibilities for treatment of other viral diseases. PMOs are highly stable, are effective by a variety of routes of administration, can be readily formulated in common isotonic delivery vehicles, and can be rapidly designed and synthesized. These are properties which may make PMOs good candidates for use during responses to emerging or reemerging viruses that may be insensitive to available therapies or for use during outbreaks, especially in regions that lack a modern medical infrastructure. While the efficacy of sequence-specific therapies can be limited by target-site sequence variations that occur between variants or by the emergence of resistant mutants during infections, various PMO design strategies can minimize these impacts. These strategies include the use of promiscuous bases such as inosine to compensate for predicted base-pair mismatches, the use of sequences that target conserved sites between viral strains, and the use of sequences that target host products that viruses utilize for infection.

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Enhanced inhibition of porcine reproductive and respiratory syndrome virus replication by combination of morpholino oligomers

Cited by 19 publications

References 26 publications

Lipid rafts both in cellular membrane and viral envelope are critical for PRRSV efficient infection

Lipid rafts both in cellular membrane and viral envelope are critical for PRRSV efficient infection

Tilmicosin Reduces PRRSV Loads in Pigs in vivo

Advanced morpholino oligomers: A novel approach to antiviral therapy

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