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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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Analysis of tissue 38 days post contact infection by LCM in combination with quantitative rRT-PCR.FMDV copies per 108 copies of 28 s rRNA of GC samples positive for FMDV by quantitative rRT-PCR versus tissue type from cattle 38 days post contact infection (n = 4 animals. Adjusted means±standard error of the mean; ANOVA, general linear model). Approximately 100 bovine peripheral blood mononuclear cells contain 108 copies of 28 s rRNA. There was a statistically significant association between the quantity of FMDV genome present in GC samples and type of tissue (p = 0.0039, Fisher's exact test).
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pone-0003434-g001: Analysis of tissue 38 days post contact infection by LCM in combination with quantitative rRT-PCR.FMDV copies per 108 copies of 28 s rRNA of GC samples positive for FMDV by quantitative rRT-PCR versus tissue type from cattle 38 days post contact infection (n = 4 animals. Adjusted means±standard error of the mean; ANOVA, general linear model). Approximately 100 bovine peripheral blood mononuclear cells contain 108 copies of 28 s rRNA. There was a statistically significant association between the quantity of FMDV genome present in GC samples and type of tissue (p = 0.0039, Fisher's exact test).

Mentions: Germinal centre (GC) and non-GC regions of the dorsal surface of the palatum molle (dorsal soft palates), pharyngeal tonsils [8], palatine tonsils, lateral retropharyngeal lymph nodes and mandibular lymph nodes obtained from four cattle 38 days post contact exposure to FMDV serotype O were selected for laser capture microdissection (LCM, Table 1, Figure S1). FMDV genome was detected consistently by quantitative rRT-PCR within the GC samples obtained by LCM (Figure S2 to S6). No FMDV genome was detected in the epithelium of the dorsal soft palates and pharyngeal tonsils (Figure S2 to S3). No FMDV genome was detected in the crypt epithelium, glandular epithelium and interfollicular regions of the palatine tonsils or the interfollicular regions of the mandibular lymph nodes and lateral retropharyngeal lymph nodes (Figure S4 to S6). No FMDV genome could be detected in GC samples obtained by LCM from non-infected control animals (data not shown). Significantly more FMDV genome copies per 108 copies of 28 s rRNA were detected in replicates of six GCs from mandibular lymph nodes, compared to similar replicates harvested from other tissue (Figure 1) (Mandibular lymph node compared to lateral retropharyngeal lymph node [p = 0.0014], mandibular lymph node compared to palatine tonsil [p = 0.0376], mandibular lymph node compared to pharyngeal tonsil [p = 0.0392] and mandibular lymph node compared to dorsal soft palate [p = 0.0148]; ANOVA, Tukey simultaneous test).


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)

Analysis of tissue 38 days post contact infection by LCM in combination with quantitative rRT-PCR.FMDV copies per 108 copies of 28 s rRNA of GC samples positive for FMDV by quantitative rRT-PCR versus tissue type from cattle 38 days post contact infection (n = 4 animals. Adjusted means±standard error of the mean; ANOVA, general linear model). Approximately 100 bovine peripheral blood mononuclear cells contain 108 copies of 28 s rRNA. There was a statistically significant association between the quantity of FMDV genome present in GC samples and type of tissue (p = 0.0039, Fisher's exact test).
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2563691&req=5

pone-0003434-g001: Analysis of tissue 38 days post contact infection by LCM in combination with quantitative rRT-PCR.FMDV copies per 108 copies of 28 s rRNA of GC samples positive for FMDV by quantitative rRT-PCR versus tissue type from cattle 38 days post contact infection (n = 4 animals. Adjusted means±standard error of the mean; ANOVA, general linear model). Approximately 100 bovine peripheral blood mononuclear cells contain 108 copies of 28 s rRNA. There was a statistically significant association between the quantity of FMDV genome present in GC samples and type of tissue (p = 0.0039, Fisher's exact test).
Mentions: Germinal centre (GC) and non-GC regions of the dorsal surface of the palatum molle (dorsal soft palates), pharyngeal tonsils [8], palatine tonsils, lateral retropharyngeal lymph nodes and mandibular lymph nodes obtained from four cattle 38 days post contact exposure to FMDV serotype O were selected for laser capture microdissection (LCM, Table 1, Figure S1). FMDV genome was detected consistently by quantitative rRT-PCR within the GC samples obtained by LCM (Figure S2 to S6). No FMDV genome was detected in the epithelium of the dorsal soft palates and pharyngeal tonsils (Figure S2 to S3). No FMDV genome was detected in the crypt epithelium, glandular epithelium and interfollicular regions of the palatine tonsils or the interfollicular regions of the mandibular lymph nodes and lateral retropharyngeal lymph nodes (Figure S4 to S6). No FMDV genome could be detected in GC samples obtained by LCM from non-infected control animals (data not shown). Significantly more FMDV genome copies per 108 copies of 28 s rRNA were detected in replicates of six GCs from mandibular lymph nodes, compared to similar replicates harvested from other tissue (Figure 1) (Mandibular lymph node compared to lateral retropharyngeal lymph node [p = 0.0014], mandibular lymph node compared to palatine tonsil [p = 0.0376], mandibular lymph node compared to pharyngeal tonsil [p = 0.0392] and mandibular lymph node compared to dorsal soft palate [p = 0.0148]; ANOVA, Tukey simultaneous test).

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