Porcine reproductive and respiratory syndrome virus (PRRSV) is an important arterivirus that can cause significant losses in swine industry. At present, there are no adequate control strategies against PRRSV. Thus, there is an urgent need for new treatment regimens that have efficacious antiviral activity to compensate for vaccines. Cryptoporus volvatus commonly serves as an anti-infective agent in Tradational Chinese Medicines. In this report, we exploited whether the aqueous extract from the fruiting body of Cryptoporus volvatus had the potential to inhibit PRRSV infection. Our results showed that the extract significantly inhibited PRRSV infection by repressing virus entry, viral RNA expression, and possibly viral protein synthesis, cell-to-cell spread, and releasing of virus particles. However, it did not block PRRSV binding to cells. Further studies confirmed that the extract directly inhibited PRRSV RNA-dependent RNA polymerase (RdRp) activity, thus interfering with PRRSV RNA and protein synthesis. More importantly, the extract efficiently inhibited highly pathologic PRRSV (HP-PRRSV) infection in vivo, reduced virus load in serum, and increased the survival rate of pigs inoculated with HP-PRRSV strain. Collectively, our findings imply that the aqueous extract from the fruiting body of Cryptoporus volvatus has the potential to be used for anti-PRRSV therapies.
References
[1]
Neumann EJ, Kliebenstein JB, Johnson CD, Mabry JW, Bush EJ, et al. (2005) Assessment of the economic impact of porcine reproductive and respiratory syndrome on swine production in the United States. J Am Vet Med Assoc 227(3): 385–392.
[2]
Tian K, Yu X, Zhao T, Feng Y, Cao Z, et al. (2007) Emergence of fatal PRRSV variants: unparalleled outbreaks of atypical PRRS in China and molecular dissection of the unique hallmark. PLoS One 2: e526.
[3]
Li Y, Wang X, Bo K, Tang B, Yang B, et al. (2007) Emergence of a highly pathogenic porcine reproductive and respiratory syndrome virus in the Mid-Eastern region of China. Vet J 174: 577–584.
[4]
Zhou YJ, Hao XF, Tian ZJ, Tong GZ, Yoo D, et al. (2008) Highly virulent porcine reproductive and respiratory syndrome virus emerged in China. Transbound Emerg Dis 55: 152–164.
[5]
Ni J, Yang S, Bounlom D, Yu X, Zhou Z, et al. (2012) Emergence and pathogenicity of highly pathogenic Porcine reproductive and respiratory syndrome virus in Vientiane, Lao People’s Democratic Republic. J Vet Diagn Invest 24: 349–354.
[6]
Zhou L, Zhang J, Zeng J, Yin S, Li Y, et al. (2009) The 30-amino-acid deletion in the Nsp2 of highly pathogenic porcine reproductive and respiratory syndrome virus emerging in China is not related to its virulence. J Virol 83: 5156–5167.
[7]
Gorbalenya AE, Enjuanes L, Ziebuhr J, Snijder EJ (2006) Nidovirales: evolving the largest RNA virus genome. Virus Res 117: 17–37.
[8]
Snijder EJ, Meulenberg JJ (1998) The molecular biology of arteriviruses. J Gen Virol 79 (Pt 5): 961–979.
[9]
Firth AE, Zevenhoven-Dobbe JC, Wills NM, Go YY, Balasuriya UB, et al. (2011) Discovery of a small arterivirus gene that overlaps the GP5 coding sequence and is important for virus production. J Gen Virol 92: 1097–1106.
[10]
Johnson CR, Griggs TF, Gnanandarajah J, Murtaugh MP (2011) Novel structural protein in porcine reproductive and respiratory syndrome virus encoded by an alternative ORF5 present in all arteriviruses. J Gen Virol 92: 1107–1116.
[11]
Pedersen KW, van der Meer Y, Roos N, Snijder EJ (1999) Open reading frame 1a-encoded subunits of the arterivirus replicase induce endoplasmic reticulum-derived double-membrane vesicles which carry the viral replication complex. J Virol 73: 2016–2026.
[12]
Murtaugh MP, Genzow M (2011) Immunological solutions for treatment and prevention of porcine reproductive and respiratory syndrome (PRRS). Vaccine 29: 8192–8204.
[13]
Storgaard T, Oleksiewicz M, Botner A (1999) Examination of the selective pressures on a live PRRS vaccine virus. Arch Virol 144: 2389–2401.
[14]
Karuppannan AK, Wu KX, Qiang J, Chu JJ, Kwang J (2012) Natural compounds inhibiting the replication of Porcine reproductive and respiratory syndrome virus. Antiviral Res 94: 188–194.
[15]
Zjawiony JK (2004) Biologically active compounds from Aphyllophorales (polypore) fungi. J Nat Prod 67: 300–310.
[16]
Stamets P (2006) Can mushrooms help save the world? Interview by Bonnie J. Horrigan. Explore (NY) 2: 152–161.
[17]
Wasser SP (2011) Current findings, future trends, and unsolved problems in studies of medicinal mushrooms. Appl Microbiol Biotechnol 89: 1323–1332.
[18]
Lindequist U, Niedermeyer TH, Julich WD (2005) The pharmacological potential of mushrooms. Evid Based Complement Alternat Med 2: 285–299.
[19]
Faccin LC, Benati F, Rincao VP, Mantovani MS, Soares SA, et al. (2007) Antiviral activity of aqueous and ethanol extracts and of an isolated polysaccharide from Agaricus brasiliensis against poliovirus type 1. Lett Appl Microbiol 45: 24–28.
[20]
Mothana RA, Awadh Ali NA, Jansen R, Wegner U, Mentel R, et al. (2003) Antiviral lanostanoid triterpenes from the fungus Ganoderma pfeifferi. Fitoterapia 74: 177–180.
[21]
Yamamoto KA, Galhardi LC, Rincao VP, Soares SD, Vieira IG, et al. (2012) Antiherpetic activity of an Agaricus brasiliensis polysaccharide, its sulfated derivative and fractions. Int J Biol Macromol 52C: 9–13.
[22]
Xu J (1997) Chinese medicinal mycology. Beijing: publishing house of Peking Union Medical College and China Medical University. 836 p.
[23]
Wu ZY (1990) Xin-Hua Compendium of Materia Medica. Shanghai: Shanghai Science and Technology Publishing House. 735 p.
[24]
Wu JZ GJ, Huang NL (1999) et.al (1999) Fermentation Culture & Analysis of Compositions of Cryptoporus Volvatus (Peck) Schear. Journal of Fujian College of TCM 9(1): 33–36.
[25]
Jin SH, Xie QM, Lin XX, Deng YM, Chen JQ (2003) [Effect of Cryptoporus volvatus (Peck) Schear on leukotriene production from polymorphonuclear leukocytes in rats]. Zhongguo Zhong Yao Za Zhi 28: 650–653.
Xie QM, Deng JF, Deng YM, Shao CS, Zhang H, et al. (2006) Effects of cryptoporus polysaccharide on rat allergic rhinitis associated with inhibiting eotaxin mRNA expression. J Ethnopharmacol 107: 424–430.
[28]
Kim HS, Kwang J, Yoon IJ, Joo HS, Frey ML (1993) Enhanced replication of porcine reproductive and respiratory syndrome (PRRS) virus in a homogeneous subpopulation of MA-104 cell line. Arch Virol 133: 477–483.
[29]
Quinting B, Robert B, Letellier C, Boxus M, Kerkhofs P, et al. (2007) Development of a 1-step enzyme-linked immunosorbent assay for the rapid diagnosis of bovine respiratory syncytial virus in postmortem specimens. J Vet Diagn Invest 19: 238–243.
[30]
Luo R, Fang L, Jin H, Jiang Y, Wang D, et al. (2011) Antiviral activity of type I and type III interferons against porcine reproductive and respiratory syndrome virus (PRRSV). Antiviral Res 91: 99–101.
[31]
Wootton S, Yoo D, Rogan D (2000) Full-length sequence of a Canadian porcine reproductive and respiratory syndrome virus (PRRSV) isolate. Arch Virol 145: 2297–2323.
[32]
Beerens N, Selisko B, Ricagno S, Imbert I, van der Zanden L, et al. (2007) De novo initiation of RNA synthesis by the arterivirus RNA-dependent RNA polymerase. J Virol 81: 8384–8395.
[33]
Panicali DL, Nair CN (1978) Effect of cordycepin triphosphate on in vitro RNA synthesis by picornavirus polymerase complexes. J Virol 25: 124–128.
[34]
White JL, Dawson WO (1979) Effect of cordycepin triphosphate on in vitro RNA synthesis by plant viral replicases. J Virol 29: 811–814.
[35]
Kreutz LC, Ackermann MR (1996) Porcine reproductive and respiratory syndrome virus enters cells through a low pH-dependent endocytic pathway. Virus Res 42: 137–147.
[36]
Nauwynck HJ, Duan X, Favoreel HW, Van Oostveldt P, Pensaert MB (1999) Entry of porcine reproductive and respiratory syndrome virus into porcine alveolar macrophages via receptor-mediated endocytosis. J Gen Virol 80 (Pt 2): 297–305.
[37]
Kumar N, Liang Y, Parslow TG (2011) Receptor tyrosine kinase inhibitors block multiple steps of influenza a virus replication. J Virol 85: 2818–2827.
[38]
Misumi Y, Miki K, Takatsuki A, Tamura G, Ikehara Y (1986) Novel blockade by brefeldin A of intracellular transport of secretory proteins in cultured rat hepatocytes. J Biol Chem 261: 11398–11403.
[39]
Sattentau Q (2008) Avoiding the void: cell-to-cell spread of human viruses. Nat Rev Microbiol 6: 815–826.
[40]
Sattentau QJ (2011) The direct passage of animal viruses between cells. Curr Opin Virol 1: 396–402.
[41]
Cafruny WA, Duman RG, Wong GH, Said S, Ward-Demo P, et al. (2006) Porcine reproductive and respiratory syndrome virus (PRRSV) infection spreads by cell-to-cell transfer in cultured MARC-145 cells, is dependent on an intact cytoskeleton, and is suppressed by drug-targeting of cell permissiveness to virus infection. Virol J 3: 90.
[42]
Harvey AL (2008) Natural products in drug discovery. Drug Discov Today 13: 894–901.
[43]
Tomei L, Altamura S, Bartholomew L, Bisbocci M, Bailey C, et al. (2004) Characterization of the inhibition of hepatitis C virus RNA replication by nonnucleosides. J Virol 78: 938–946.
[44]
Gastaminza P, Whitten-Bauer C, Chisari FV (2010) Unbiased probing of the entire hepatitis C virus life cycle identifies clinical compounds that target multiple aspects of the infection. Proc Natl Acad Sci U S A 107: 291–296.
[45]
Guo XK, Zhang Q, Gao L, Li N, Chen XX, et al. (14 Nov 2012) Additional expression of microRNA-181 inhibits Porcine Reproductive and Respiratory Syndrome Virus replication and its implications for controlling virus infection. J Virol: doi:10.1128/JVI.02386–02312.
[46]
Balzarini J, Pelemans H, Karlsson A, De Clerc QE, Kleim JP (1996) Concomitant combination therapy for HIV infection preferable over sequential therapy with 3TC and non-nucleoside reverse transcriptase inhibitors. Proc Natl Acad Sci U S A 93: 13152–13157.