The Infectivity of prM-Containing Partially Mature West Nile Virus Does Not Require the Activity of Cellular Furin-Like Proteases

Viral Pathogenesis Section, Laboratory of Viral Diseases, National Institutes of Health, 33 North Drive, Building 33, Room 2E19A.2, Bethesda, MD 20892, USA.
Journal of Virology (Impact Factor: 4.44). 08/2011; 85(22):12067-72. DOI: 10.1128/JVI.05559-11
Source: PubMed


Cleavage of the flavivirus prM protein by a cellular furin-like protease is a hallmark of virion maturation. While this cleavage is a required step in the viral life cycle, it can be inefficient. Virions that retain uncleaved prM may be infectious. We investigated whether cleavage by furin of prM on partially mature West Nile virus (WNV) during virus entry contributes to infectivity. Using quantitative assays of WNV infection, we found that virions incorporating considerable amounts of uncleaved prM protein were insensitive to treatment of cells with a potent inhibitor of furin activity. Thus, partially mature WNV does not require furin-like proteases for infectivity.

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Available from: Swati Mukherjee, Dec 21, 2013
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    • "Early studies suggested that complete maturation is necessary to render flavivirus particles infectious (Stadler et al., 1997). However, recent studies have demonstrated that not only are virions retaining uncleaved prM infectious (Colpitts et al., 2011; Mukherjee et al., 2011; Nelson et al., 2008; Zybert et al., 2008), but that complete maturation may be detrimental to WNV replication under certain circumstances (Zybert et al., 2008). Whilst most strains of WNV contain a glycosylation site in both E and the precursor portion of prM, some non-pathogenic strains lack the E glycosylation site. "
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    • "Therefore, immature particles are presumably scored non-infectious in numerous cell lines like K562, U937, THP-1, P388D1, and human PBMCs [17], [22], [25]. However, and in line with recent results on WNV [26], we here show that immature DENV is infectious in cells expressing DC-SIGN. Binding of immature particles to DC-SIGN is presumably facilitated by sugar groups linked to position Asn69 on prM, or sugar groups linked to position Asn67 and Asn153 on E [15], [16], [26], [28]. "
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    • "This orchestrates profound rearrangements of viral glycoproteins that result in the acquisition of the mature structure of the virion [14], [15], [16]. While this cleavage is a required step in the viral life cycle, it can be inefficient; suggesting that complete maturation is not required for infectivity [17], [18]. Indeed, the presence of flaviviral ‘mosaic’ particles combining regions of mature and immature structure has been documented [19], and the degree of maturation of flavivirus particles has been related to different aspects of their interaction with antibodies [18], [20], [21], [22]. "
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