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Griffithsin inhibits porcine reproductive and respiratory syndrome virus infection in vitro.

ABSTRACT: Porcine reproductive and respiratory syndrome virus (PRRSV) is a pathogen that severely disrupts swine production. Despite sustained efforts, the disease is still endemic, with high mortality and morbidity. New antiviral strategies to control PRRSV are needed. Griffithsin, a red algal lectin, has potent antiviral effect on several human enveloped viruses, but this effect has not been demonstrated on PRRSV. Here, we first tested the in vitro antiviral activity of Griffithsin against PRRSV. Griffithsin exerted strong saccharide-dependent antiviral activity against PRRSV, probably through interactions with glycans on the surface of PRRSV that interfered with virus entry. Furthermore we revealed that Griffithsin's action on PRRSV involved blocking viral adsorption, and it had no effect on viral penetration. Besides Our findings also suggested that Griffithsin may interfere with cell-to-cell spread to prevent virus transmission. The remarkable potency profile of Griffithsin supports its potential value as an antiviral agent against PRRSV.

SUBMITTER: Li L

PROVIDER: S-EPMC7087274 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Griffithsin inhibits porcine reproductive and respiratory syndrome virus infection in vitro.

Li Lan L Tian Xiaoning X Chen Jin J Li Pengcheng P Zheng Qisheng Q Hou Jibo J

Archives of virology 20180915 12

Porcine reproductive and respiratory syndrome virus (PRRSV) is a pathogen that severely disrupts swine production. Despite sustained efforts, the disease is still endemic, with high mortality and morbidity. New antiviral strategies to control PRRSV are needed. Griffithsin, a red algal lectin, has potent antiviral effect on several human enveloped viruses, but this effect has not been demonstrated on PRRSV. Here, we first tested the in vitro antiviral activity of Griffithsin against PRRSV. Griffi ...[more]

PMID: 30220033

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Project description:Studying viral glycoprotein-host membrane protein interactions contributes to the discovery of novel cell receptors or entry facilitators for viruses. Glycoprotein 5 (GP5), which is a major envelope protein of porcine reproductive and respiratory syndrome virus (PRRSV) virions, is a key target for the control of the virus. Here, the macrophage receptor with collagenous structure (MARCO), which is a member of the scavenger receptor family, was identified as one of the host interactors of GP5 through a DUALmembrane yeast two-hybrid screening. MARCO was specifically expressed on porcine alveolar macrophages (PAMs), and PRRSV infection downregulated MARCO expression both in vitro and in vivo. MARCO was not involved in viral adsorption and internalization processes, indicating that MARCO may not be a PRRSV-entry facilitator. Contrarily, MARCO served as a host restriction factor for PRRSV. The knockdown of MARCO in PAMs enhanced PRRSV proliferation, whereas overexpression suppressed viral proliferation. The N-terminal cytoplasmic region of MARCO was responsible for its inhibitory effect on PRRSV. Further, we found that MARCO was a proapoptotic factor in PRRSV-infected PAMs. MARCO knockdown weakened virus-induced apoptosis, whereas overexpression aggravated apoptosis. MARCO aggravated GP5-induced apoptosis, which may result in its proapoptotic function in PAMs. The interaction between MARCO and GP5 may contribute to the intensified apoptosis induced by GP5. Additionally, the inhibition of apoptosis during PRRSV infection weakened the antiviral function of MARCO, suggesting that MARCO inhibits PRRSV through the regulation of apoptosis. Taken together, the results of this study reveal a novel antiviral mechanism of MARCO and suggest a molecular basis for the potential development of therapeutics against PRRSV. IMPORTANCE Porcine reproductive and respiratory syndrome virus (PRRSV) has been one of the most serious threats to the global swine industry. Glycoprotein 5 (GP5) exposed on the surface of PRRSV virions is a major glycoprotein, and it is involved in viral entry into host cells. A macrophage receptor with collagenous structure (MARCO), which is a member of the scavenger receptor family, was identified to interact with PRRSV GP5 in a DUALmembrane yeast two-hybrid screening. Further investigation demonstrated that MARCO may not serve as a potential receptor to mediate PRRSV entry. Instead, MARCO was a host restriction factor for the virus, and the N-terminal cytoplasmic region of MARCO was responsible for its anti-PRRSV effect. Mechanistically, MARCO inhibited PRRSV infection through intensifying virus-induced apoptosis in PAMs. The interaction between MARCO and GP5 may contribute to GP5-induced apoptosis. Our work reveals a novel antiviral mechanism of MARCO and advances the development of control strategies for the virus.

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Griffithsin inhibits porcine reproductive and respiratory syndrome virus infection in vitro.

Publications

Griffithsin inhibits porcine reproductive and respiratory syndrome virus infection in vitro.

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