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Foot-and-mouth disease virus persists in the light zone of germinal centres.

Juleff N, Windsor M, Reid E, Seago J, Zhang Z, Monaghan P, Morrison IW, Charleston B - PLoS ONE (2008)

Bottom Line: Two fundamental problems remain to be understood before more effective control measures can be put in place.These problems are the FMDV "carrier state" and the short duration of immunity after vaccination which contrasts with prolonged immunity after natural infection.We propose that maintenance of non-replicating FMDV in these sites represents a source of persisting infectious virus and also contributes to the generation of long-lasting antibody responses against neutralising epitopes of the virus.

View Article: PubMed Central - PubMed

Affiliation: Pirbright Laboratory, Institute for Animal Health, Woking, Surrey, United Kingdom. nicholas.juleff@bbsrc.ac.uk

ABSTRACT
Foot-and-mouth disease virus (FMDV) is one of the most contagious viruses of animals and is recognised as the most important constraint to international trade in animals and animal products. Two fundamental problems remain to be understood before more effective control measures can be put in place. These problems are the FMDV "carrier state" and the short duration of immunity after vaccination which contrasts with prolonged immunity after natural infection. Here we show by laser capture microdissection in combination with quantitative real-time reverse transcription polymerase chain reaction, immunohistochemical analysis and corroborate by in situ hybridization that FMDV locates rapidly to, and is maintained in, the light zone of germinal centres following primary infection of naïve cattle. We propose that maintenance of non-replicating FMDV in these sites represents a source of persisting infectious virus and also contributes to the generation of long-lasting antibody responses against neutralising epitopes of the virus.

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Tissue localisation of FMDV proteins 29–38 days post infection.Mandibular lymph node GC sections 38 days post contact infection. (A) FMDV capsid labelled green with MAb IB11, dark zone FDCs labelled red with MAb D46 [13]. (B) dark zone FDCs labelled red with MAb D46, no signal detected with isotype primary control MAb TRT1 labelled green [38]. (C) No signal detected with FMDV non-structural protein 3A labelled green with MAb 2C2 [10]. FMDV non-structural proteins could not be detected by immunohistochemical analysis of tissue from 29 to 38 days post contact infection. (D) No primary or secondary antibodies highlighting autofluorescence associated with bovine GCs. (E) High power image of (A). Nuclei stained blue (DAPI), scale bars = 100 µm.
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pone-0003434-g003: Tissue localisation of FMDV proteins 29–38 days post infection.Mandibular lymph node GC sections 38 days post contact infection. (A) FMDV capsid labelled green with MAb IB11, dark zone FDCs labelled red with MAb D46 [13]. (B) dark zone FDCs labelled red with MAb D46, no signal detected with isotype primary control MAb TRT1 labelled green [38]. (C) No signal detected with FMDV non-structural protein 3A labelled green with MAb 2C2 [10]. FMDV non-structural proteins could not be detected by immunohistochemical analysis of tissue from 29 to 38 days post contact infection. (D) No primary or secondary antibodies highlighting autofluorescence associated with bovine GCs. (E) High power image of (A). Nuclei stained blue (DAPI), scale bars = 100 µm.

Mentions: The anti-FMDV capsid MAbs gave a diffuse punctate pattern of positive labelling which was restricted to GCs within lymphoid tissue and confined to the light zone within the GC from 29 days post infection (Table 2, Figure 3, 4 and S15). By contrast, the FMDV non-structural proteins 3A and 3C could not be detected in any of the tissues from animals after 28 days post contact infection (Table 2, Figure 3) [10], [11]. Antibodies specific for 3A and 3C readily detected infected cells in FMDV vesicles and lymph tissue during the acute phase of infection and in infected BHK-21 cells, co-localising with FMDV capsid (Figure S11 to S13). Also, using immunofluorescence confocal microscopy there was a lack of labelling for the dominant FMDV cellular receptor, αvβ6 integrin [12], in the GCs (Figure S16). The diffuse punctate pattern of labelled viral capsid was shown to be localised to the light zone follicular dendritic cell (FDC) network by co-labelling with an antibody specific for light zone FDCs (Figure 4) [13]. Detailed analysis of in situ hybridization and immunohistochemistry showed a consistent punctate pattern (Figure S15). The punctate labelling pattern observed in Figure S15 panel D is consistent with the distribution pattern of iccosomes on FDCs [14]. This pattern is in contrast to the diffuse cytoplasmic labelling pattern of cells observed during acute infection in vivo and in infected cells in vitro (Compare Figures 3 and 4 with Figure S11 to S13).


Foot-and-mouth disease virus persists in the light zone of germinal centres.

Juleff N, Windsor M, Reid E, Seago J, Zhang Z, Monaghan P, Morrison IW, Charleston B - PLoS ONE (2008)

Tissue localisation of FMDV proteins 29–38 days post infection.Mandibular lymph node GC sections 38 days post contact infection. (A) FMDV capsid labelled green with MAb IB11, dark zone FDCs labelled red with MAb D46 [13]. (B) dark zone FDCs labelled red with MAb D46, no signal detected with isotype primary control MAb TRT1 labelled green [38]. (C) No signal detected with FMDV non-structural protein 3A labelled green with MAb 2C2 [10]. FMDV non-structural proteins could not be detected by immunohistochemical analysis of tissue from 29 to 38 days post contact infection. (D) No primary or secondary antibodies highlighting autofluorescence associated with bovine GCs. (E) High power image of (A). Nuclei stained blue (DAPI), scale bars = 100 µm.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2563691&req=5

pone-0003434-g003: Tissue localisation of FMDV proteins 29–38 days post infection.Mandibular lymph node GC sections 38 days post contact infection. (A) FMDV capsid labelled green with MAb IB11, dark zone FDCs labelled red with MAb D46 [13]. (B) dark zone FDCs labelled red with MAb D46, no signal detected with isotype primary control MAb TRT1 labelled green [38]. (C) No signal detected with FMDV non-structural protein 3A labelled green with MAb 2C2 [10]. FMDV non-structural proteins could not be detected by immunohistochemical analysis of tissue from 29 to 38 days post contact infection. (D) No primary or secondary antibodies highlighting autofluorescence associated with bovine GCs. (E) High power image of (A). Nuclei stained blue (DAPI), scale bars = 100 µm.
Mentions: The anti-FMDV capsid MAbs gave a diffuse punctate pattern of positive labelling which was restricted to GCs within lymphoid tissue and confined to the light zone within the GC from 29 days post infection (Table 2, Figure 3, 4 and S15). By contrast, the FMDV non-structural proteins 3A and 3C could not be detected in any of the tissues from animals after 28 days post contact infection (Table 2, Figure 3) [10], [11]. Antibodies specific for 3A and 3C readily detected infected cells in FMDV vesicles and lymph tissue during the acute phase of infection and in infected BHK-21 cells, co-localising with FMDV capsid (Figure S11 to S13). Also, using immunofluorescence confocal microscopy there was a lack of labelling for the dominant FMDV cellular receptor, αvβ6 integrin [12], in the GCs (Figure S16). The diffuse punctate pattern of labelled viral capsid was shown to be localised to the light zone follicular dendritic cell (FDC) network by co-labelling with an antibody specific for light zone FDCs (Figure 4) [13]. Detailed analysis of in situ hybridization and immunohistochemistry showed a consistent punctate pattern (Figure S15). The punctate labelling pattern observed in Figure S15 panel D is consistent with the distribution pattern of iccosomes on FDCs [14]. This pattern is in contrast to the diffuse cytoplasmic labelling pattern of cells observed during acute infection in vivo and in infected cells in vitro (Compare Figures 3 and 4 with Figure S11 to S13).

Bottom Line: Two fundamental problems remain to be understood before more effective control measures can be put in place.These problems are the FMDV "carrier state" and the short duration of immunity after vaccination which contrasts with prolonged immunity after natural infection.We propose that maintenance of non-replicating FMDV in these sites represents a source of persisting infectious virus and also contributes to the generation of long-lasting antibody responses against neutralising epitopes of the virus.

View Article: PubMed Central - PubMed

Affiliation: Pirbright Laboratory, Institute for Animal Health, Woking, Surrey, United Kingdom. nicholas.juleff@bbsrc.ac.uk

ABSTRACT
Foot-and-mouth disease virus (FMDV) is one of the most contagious viruses of animals and is recognised as the most important constraint to international trade in animals and animal products. Two fundamental problems remain to be understood before more effective control measures can be put in place. These problems are the FMDV "carrier state" and the short duration of immunity after vaccination which contrasts with prolonged immunity after natural infection. Here we show by laser capture microdissection in combination with quantitative real-time reverse transcription polymerase chain reaction, immunohistochemical analysis and corroborate by in situ hybridization that FMDV locates rapidly to, and is maintained in, the light zone of germinal centres following primary infection of naïve cattle. We propose that maintenance of non-replicating FMDV in these sites represents a source of persisting infectious virus and also contributes to the generation of long-lasting antibody responses against neutralising epitopes of the virus.

Show MeSH
Related in: MedlinePlus