Pathogenesis of foot-and-mouth disease: the lung as an additional portal of entry of the virus

Sutmöller, P.; McVicar, J. W.

doi:10.1017/s0022172400024669

Cited by 33 publications

(24 citation statements)

References 14 publications

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“…It causes viremia, and there is evidence that spread through the bloodstream is important in the dissemination of the virus within the animal (48). Wild-type isolates of FMDV do not bind to HS, but upon tissue culture passaging, SP variants with the ability to bind to HS arise (18,43).…”

Section: Discussionmentioning

confidence: 99%

Large-Plaque Mutants of Sindbis Virus Show Reduced Binding to Heparan Sulfate, Heightened Viremia, and Slower Clearance from the Circulation

Byrnes¹,

Griffin

2000

J Virol

115

101

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Laboratory strains of Sindbis virus must bind to the negatively charged glycosaminoglycan heparan sulfate in order to efficiently infect cultured cells. During infection of mice, however, we have frequently observed the development of large-plaque viral mutants with a reduced ability to bind to heparan sulfate. Sequencing of these mutants revealed changes of positively charged amino acids in putative heparin-binding domains of the E2 glycoprotein. Recombinant viruses were constructed with these changes as single amino acid substitutions in a strain Toto 1101 background. All exhibited decreased binding to heparan sulfate and had larger plaques than Toto 1101. When injected subcutaneously into neonatal mice, large-plaque viruses produced higher-titer viremia and often caused higher mortality. Because circulating heparin-binding proteins are known to be rapidly sequestered by tissue heparan sulfate, we measured the kinetics of viral clearance following intravenous injection. Much of the parental small-plaque Toto 1101 strain of Sindbis virus was cleared from the circulation by the liver within minutes, in contrast to recombinant large-plaque viruses, which had longer circulating half-lives. These findings indicate that a decreased ability to bind to heparan sulfate allows more efficient viral production in vivo, which may in turn lead to increased mortality. Because Sindbis virus is only one of a growing number of viruses from many families which have been shown to bind to heparan sulfate, these results may be generally applicable to the pathogenesis of such viruses.The alphaviruses are RNA viruses which are carried by hematophagous insects, such as mosquitoes, and can infect a wide variety of mammalian and avian hosts. In vertebrates, they can replicate extremely rapidly and cause high-titer viremia, which allows transmission of the virus to new mosquitoes. Sindbis virus (SV) is a particularly well-studied alphavirus which causes a mild rash and arthritis in humans but can cause fatal encephalomyelitis in mice.The cell surface receptors which allow alphaviruses such as SV to infect such a broad variety of species have not yet been conclusively determined, but it has recently been shown that SV can attach to heparan sulfate (HS), a negatively charged glycosaminoglycan expressed on many types of cells (4,23,32). Sulfated glycosaminoglycans on the cell surface and in the extracellular matrix normally bind a wide variety of growth factors, chemokines, enzymes, and matrix components (30, 45) but are also important in the attachment of a number of bacteria, protozoa, and viruses (42). Proteins typically bind electrostatically to HS by use of stretches of positively charged amino acids such as Lys and Arg, and attachment of SV to HS is presumably mediated in the same fashion. Although the use of cell surface HS greatly increases the efficiency of SV attachment, it is not absolutely required for infection, and a distantly related Alphavirus, Ross River virus, does not bind HS at all (4). It has been proposed that the abil...

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Section: Discussionmentioning

confidence: 99%

Large-Plaque Mutants of Sindbis Virus Show Reduced Binding to Heparan Sulfate, Heightened Viremia, and Slower Clearance from the Circulation

Byrnes¹,

Griffin

2000

J Virol

115

101

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“…Infected cattle also aerosolize large amounts of virus, which can infect other cattle in addition to other species (438). A number of studies have suggested that the lung or pharyngeal areas are the sites of initial virus replication (72,79,444), with rapid dissemination of the virus to oral and pedal epithelial areas (72,79,444), possibly mediated by cells of monocyte/macrophage origin (72). In cattle experimentally infected via aerosol, it was found, by in situ hybridization (ISH), that within the first 24 h, virus was present in respiratory bronchiolar epithelium, subepithelium, and interstitial areas of the lung (74).…”

Section: Pathogenesismentioning

confidence: 99%

Foot-and-Mouth Disease

2004

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Foot-and-mouth disease (FMD) is a highly contagious disease of cloven-hoofed animals. The disease was initially described in the 16th century and was the first animal pathogen identified as a virus. Recent FMD outbreaks in developed countries and their significant economic impact have increased the concern of governments worldwide. This review describes the reemergence of FMD in developed countries that had been disease free for many years and the effect that this has had on disease control strategies. The etiologic agent, FMD virus (FMDV), a member of the Picornaviridae family, is examined in detail at the genetic, structural, and biochemical levels and in terms of its antigenic diversity. The virus replication cycle, including virus-receptor interactions as well as unique aspects of virus translation and shutoff of host macromolecular synthesis, is discussed. This information has been the basis for the development of improved protocols to rapidly identify disease outbreaks, to differentiate vaccinated from infected animals, and to begin to identify and test novel vaccine candidates. Furthermore, this knowledge, coupled with the ability to manipulate FMDV genomes at the molecular level, has provided the framework for examination of disease pathogenesis and the development of a more complete understanding of the virus and host factors involved

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“…Moreover, the ability of FMDV to replicate in tissues of the upper respiratory system, demonstrated in early reports (7) and widely confirmed later using more sensitive approaches, identified the soft palate and pharynx as sites of FMDV replication and persistence in ruminants (8,9). Sutmoller and McVicar further expanded their initial findings to include the lung as an additional portal of virus entry (10), although many researchers considered the evidence for both sites of entry to be controversial. Recently, a detailed description of the previremic stages after experimental aerosol infection of cattle confirmed these early results, identifying both the pharynx and lung as primary sites for viral entry (11).…”

mentioning

confidence: 94%

Early Adaptive Immune Responses in the Respiratory Tract of Foot-and-Mouth Disease Virus-Infected Cattle

Pega

Bucafusco

Giacomo

et al. 2013

J Virol

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Foot-and-mouth disease (FMD) is a highly contagious viral disease which affects both domestic and wild biungulate species. This acute disease, caused by the FMD virus (FMDV), usually includes an active replication phase in the respiratory tract for up to 72 h postinfection, followed by hematogenous dissemination and vesicular lesions at oral and foot epithelia. The role of the early local adaptive immunity of the host in the outcome of the infection is not well understood. Here we report the kinetics of appearance of FMDV-specific antibody-secreting cells (ASC) in lymphoid organs along the respiratory tract and the spleen in cattle infected by aerosol exposure. While no responses were observed for up to 3 days postinfection (dpi), all animals developed FMDV-ASC in all the lymphoid organs studied at 4 dpi. Tracheobronchial lymph nodes were the most reactive organs at this time, and IgM was the predominant isotype, followed by IgG1. Numbers of FMDV-ASC were further augmented at 5 and 6 dpi, with an increasing prevalence in upper respiratory organs. Systemic antibody responses were slightly delayed compared with the local reaction. Also, IgM was the dominant isotype in serum at 5 dpi, coinciding with a sharp decrease of viral RNA detection in peripheral blood. These results indicate that following aerogenous administration, cattle develop a rapid and vigorous genuine local antibody response throughout the respiratory tract. Time course and isotype profiles indicate the presence of an efficient T cell-independent antibody response which drives the IgM-mediated virus clearance in cattle infected by FMDV aerosol exposure.

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Pathogenesis of foot-and-mouth disease: the lung as an additional portal of entry of the virus

Cited by 33 publications

References 14 publications

Large-Plaque Mutants of Sindbis Virus Show Reduced Binding to Heparan Sulfate, Heightened Viremia, and Slower Clearance from the Circulation

Large-Plaque Mutants of Sindbis Virus Show Reduced Binding to Heparan Sulfate, Heightened Viremia, and Slower Clearance from the Circulation

Foot-and-Mouth Disease

Early Adaptive Immune Responses in the Respiratory Tract of Foot-and-Mouth Disease Virus-Infected Cattle

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