West Nile virus (WNV) is a small, enveloped, single-stranded RNA virus in the family Flaviviridae. In the natural transmission cycle WNV circulates between mosquitoes as vectors and birds as reservoir hosts. Most noticeably, WNV can infect a wide taxonomical range of vertebrate species but most of them do not sufficiently support virus replication for transmission. Disease symptoms rarely occur, except in humans and horses where WNV infections are frequently accompanied by a mild fever (West Nile fever), which occasionally results in the development of neurological disorders with fatal outcome.
The cellular receptors and determinants that mediate entry of WNV are unclear to date. The notable ability of WNV to infect a broad range of species (mosquitoes, reptiles, birds and mammals), and virtually every in vitro cell line is supposed to be related to cellular proteins, relevant for virus entry and replication, which are highly conserved among divergent host species.
By using integrin knock-out cell lines which lack the particular integrin subunits, this study demonstrate that the presence of αv-, β1- or β3-integrins is not required for the attachment of four different WNV strains to the cell surface. However, β1- and β3-integrin expression significantly enhances virus amplification. These findings imply that other routes are used in the absence of these integrins, or that different routes are generally used in parallel.
Integrins modulate the infection efficiency of West Nile virus into cells. J Gen Virol. 08 May 2013
The underlying mechanisms allowing West Nile virus (WNV) to replicate in a large variety of different arthropod, bird and mammal species are largely unknown but are believed to rely on highly conserved proteins relevant for viral entry and replication. Consistent with this, the integrin αvβ3 has been proposed lately to function as the cellular receptor for WNV. More recently published data, however, are not in line with this concept. Integrins are highly conserved among diverse taxa and are expressed by almost every cell type at high numbers. Our study was designed to clarify the involvement of integrins in WNV infection of cells. A cell culture model, based on wild-type and specific integrin knock-out cell lines lacking the integrin subunits αv, β1 or β3, was used to investigate the susceptibility to WNV, and to evaluate binding and replication efficiencies of four distinct strains (New York 1999, Uganda 1937, Sarafend and Dakar). Though all cell lines were permissive, clear differences in replication efficiencies were observed. Rescue of the β3-integrin subunit resulted in enhanced WNV yields of up to 90% regardless the virus strain used. Similar results were obtained for β1-expressing and non-expressing cells. Binding, however, was not affected by the expression of the integrins in question, and integrin blocking antibodies failed to have any effect. We conclude that integrins are involved in WNV infection but not at the level of binding to target cells.