Dataset Information

Induction of partial protection against foot and mouth disease virus in guinea pigs by neutralization with the integrin ?6-1 subunit.

ABSTRACT: The mechanism by which the foot-and-mouth disease virus (FMDV) initiates infection of cells is thought to involve the attachment of the viral capsid to host integrins on the surface of target cells. However, the role of integrins in FMDV infection still needs to be fully understood, although it has been demonstrated that integrin ?v?6 interferes with FMDV in vitro and results in neutralization of its infectivity. In the present study, we describe the cloning and sequencing of suckling mouse integrin ?6 and the subsequent expression of two segments of integrin ?6 extracellular domains: ?6-1 (which contains the ligand-binding domain) and ?6-2. Sequencing of the mouse integrin ?6 subunit revealed close homology (~90%) with its human counterpart. When recombinant integrin extracellular domains ?6-1 and ?6-2 formulated with adjuvant were inoculated into guinea pigs, anti-integrin antibody expression was high before FMDV challenge. Interestingly, guinea pigs (50%) inoculated with integrin ?6-1 were protected from FMDV infection; in contrast, none of the animals inoculated with integrin ?6-2 were protected. This result indicates that an integrin blockade may be able to interfere with FMDV infection in vivo, which raises the possibility that targeting integrin in vivo may be the basis for a new strategy to control FMDV infection.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC3705268 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Induction of partial protection against foot and mouth disease virus in guinea pigs by neutralization with the integrin β6-1 subunit.

Zhang Yan Y Sun Yingjun Y Yang Fan F Guo Jianhong J He Jijun J Wu Qiong Q Cao Weijun W Lv Lv L Zheng Haixue H Zhang Zhidong Z

Viruses 20130419 4

The mechanism by which the foot-and-mouth disease virus (FMDV) initiates infection of cells is thought to involve the attachment of the viral capsid to host integrins on the surface of target cells. However, the role of integrins in FMDV infection still needs to be fully understood, although it has been demonstrated that integrin αvβ6 interferes with FMDV in vitro and results in neutralization of its infectivity. In the present study, we describe the cloning and sequencing of suckling mouse inte ...[more]

PMID: 23604096

Similar Datasets

Project description:BACKGROUND: Foot-and-mouth disease virus (FMDV) initiates infection via recognition of one of at least four cell-surface integrin molecules ?v?1, ?v?3, ?v?6, or ?v?8 by a highly conserved Arg-Gly-Asp (RGD) amino acid sequence motif located in the G-H loop of VP1. Within the animal host, the ?v?6 interaction is believed to be the most relevant. Sub-neutralizing levels of soluble secreted ?v?6 (ss?v?6) was used as a selective pressure during passages in vitro to explore the plasticity of that interaction. RESULTS: Genetically stable soluble integrin resistant (SIR) FMDV mutants derived from A24 Cruzeiro were selected after just 3 passages in cell culture in the presence of sub-neutralizing levels of ss?v?6. SIR mutants were characterized by: replication on selective cell lines, plaque morphology, relative sensitivity to ss?v?6 neutralization, relative ability to utilize ?v?6 for infection, as well as sequence and structural changes. All SIR mutants maintained an affinity for ?v?6. Some developed the ability to attach to cells expressing heparan sulfate (HS) proteoglycan, while others appear to have developed affinity for a still unknown third receptor. Two classes of SIR mutants were selected that were highly or moderately resistant to neutralization by ss?v?6. Highly resistant mutants displayed a G145D substitution (RGD to RDD), while moderately resistant viruses exhibited a L150P/R substitution at the conserved RGD + 4 position. VP1 G-H loop homology models for the A-type SIR mutants illustrated potential structural changes within the integrin-binding motif by these 2 groups of mutations. Treatment of O1 Campos with ss?v?6 resulted in 3 SIR mutants with a positively charged VP3 mutation allowing for HS binding. CONCLUSIONS: These findings illustrate how FMDV particles rapidly gain resistance to soluble receptor prophylactic measures in vitro. Two different serotypes developed distinct capsid mutations to circumvent the presence of sub-neutralizing levels of the soluble cognate receptor, all of which resulted in a modified receptor tropism that expanded the cell types susceptible to FMDV. The identification of some of these adaptive mutations in known FMDV isolates suggests these findings have implications beyond the cell culture system explored in these studies.

Dataset Information

Induction of partial protection against foot and mouth disease virus in guinea pigs by neutralization with the integrin ?6-1 subunit.

Publications

Induction of partial protection against foot and mouth disease virus in guinea pigs by neutralization with the integrin β6-1 subunit.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets