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Evaluation of immune responses following infection of ponies with an EHV-1 ORF1/2 deletion mutant.

Soboll Hussey G, Hussey SB, Wagner B, Horohov DW, Van de Walle GR, Osterrieder N, Goehring LS, Rao S, Lunn DP - Vet. Res. (2011)

Bottom Line: Infection with either virus led to cytokine responses that coincided with the course of clinical disease, particularly the biphasic pyrexia, which correlates with respiratory disease and viremia, respectively.The ΔORF1/ORF2 virus caused significantly shorter primary pyrexia and significantly reduced nasal shedding, and an attenuated decrease in PBMC IL-8 as well as increased Tbet responses compared to WT-infected ponies.In conclusion, our findings are (i) that infection of ponies with EHV-1 leads to modulation of immune responses, which are correlated with disease pathogenesis, and (ii) that the ORF1/2 genes are of importance for disease outcome and modulation of cytokine responses.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, 300 W, Drake Rd, Fort Collins, Colorado 80523, USA. husseygs@colostate.edu.

ABSTRACT
Equine herpesvirus-1 (EHV-1) infection remains a significant problem despite the widespread use of vaccines. The inability to generate a protective immune response to EHV-1 vaccination or infection is thought to be due to immunomodulatory properties of the virus, and the ORF1 and ORF2 gene products have been hypothesized as potential candidates with immunoregulatory properties. A pony infection study was performed to define immune responses to EHV-1, and to determine if an EHV-1 ORF1/2 deletion mutant (ΔORF1/2) would have different disease and immunoregulatory effects compared to wild type EHV-1 (WT). Infection with either virus led to cytokine responses that coincided with the course of clinical disease, particularly the biphasic pyrexia, which correlates with respiratory disease and viremia, respectively. Similarly, both viruses caused suppression of proliferative T-cell responses on day 7 post infection (pi). The ΔORF1/ORF2 virus caused significantly shorter primary pyrexia and significantly reduced nasal shedding, and an attenuated decrease in PBMC IL-8 as well as increased Tbet responses compared to WT-infected ponies. In conclusion, our findings are (i) that infection of ponies with EHV-1 leads to modulation of immune responses, which are correlated with disease pathogenesis, and (ii) that the ORF1/2 genes are of importance for disease outcome and modulation of cytokine responses.

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Mean clinical score, body temperature, viral nasal shedding, and viremia following infection. Clinical scores (a). Body temperatures are indicated in degree Celcius and the dotted line indicates fever (defined as a T ≥ 38.6°C) (b). Viral nasal shedding is represented as mean log gB copy numbers in nasal swabs as determined by real time PCR (c) and viremia is represented as log gB copy numbers/106 copies of β-actin in PBMCs (d). Controls (n = 5): white circles, Ab4 WT infected (n = 7): grey triangles, Ab4 delta ORF1/2 infected (n = 7): black squares. Data are displayed as means + SEM.
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Figure 2: Mean clinical score, body temperature, viral nasal shedding, and viremia following infection. Clinical scores (a). Body temperatures are indicated in degree Celcius and the dotted line indicates fever (defined as a T ≥ 38.6°C) (b). Viral nasal shedding is represented as mean log gB copy numbers in nasal swabs as determined by real time PCR (c) and viremia is represented as log gB copy numbers/106 copies of β-actin in PBMCs (d). Controls (n = 5): white circles, Ab4 WT infected (n = 7): grey triangles, Ab4 delta ORF1/2 infected (n = 7): black squares. Data are displayed as means + SEM.

Mentions: Animals in both infection groups showed signs of EHV-1 respiratory disease including pyrexia, lethargy, ocular and nasal discharge, and coughing between day 1 and day 14 pi, while none of the uninfected control animals showed any sign of clinical disease (Figure 2a). Differences in clinical scores were not significantly different between Ab4 WT- and Ab4 ΔORF1/2-infected ponies. Body temperatures are shown in Figure 2b and temperatures of both infection groups were significantly higher then in uninfected controls (p < 0.0001). The duration of the primary fever was significantly shorter in Ab4 ΔORF1/2-infected ponies compared to Ab4 WT-infected ponies (p < 0.0001).


Evaluation of immune responses following infection of ponies with an EHV-1 ORF1/2 deletion mutant.

Soboll Hussey G, Hussey SB, Wagner B, Horohov DW, Van de Walle GR, Osterrieder N, Goehring LS, Rao S, Lunn DP - Vet. Res. (2011)

Mean clinical score, body temperature, viral nasal shedding, and viremia following infection. Clinical scores (a). Body temperatures are indicated in degree Celcius and the dotted line indicates fever (defined as a T ≥ 38.6°C) (b). Viral nasal shedding is represented as mean log gB copy numbers in nasal swabs as determined by real time PCR (c) and viremia is represented as log gB copy numbers/106 copies of β-actin in PBMCs (d). Controls (n = 5): white circles, Ab4 WT infected (n = 7): grey triangles, Ab4 delta ORF1/2 infected (n = 7): black squares. Data are displayed as means + SEM.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3045331&req=5

Figure 2: Mean clinical score, body temperature, viral nasal shedding, and viremia following infection. Clinical scores (a). Body temperatures are indicated in degree Celcius and the dotted line indicates fever (defined as a T ≥ 38.6°C) (b). Viral nasal shedding is represented as mean log gB copy numbers in nasal swabs as determined by real time PCR (c) and viremia is represented as log gB copy numbers/106 copies of β-actin in PBMCs (d). Controls (n = 5): white circles, Ab4 WT infected (n = 7): grey triangles, Ab4 delta ORF1/2 infected (n = 7): black squares. Data are displayed as means + SEM.
Mentions: Animals in both infection groups showed signs of EHV-1 respiratory disease including pyrexia, lethargy, ocular and nasal discharge, and coughing between day 1 and day 14 pi, while none of the uninfected control animals showed any sign of clinical disease (Figure 2a). Differences in clinical scores were not significantly different between Ab4 WT- and Ab4 ΔORF1/2-infected ponies. Body temperatures are shown in Figure 2b and temperatures of both infection groups were significantly higher then in uninfected controls (p < 0.0001). The duration of the primary fever was significantly shorter in Ab4 ΔORF1/2-infected ponies compared to Ab4 WT-infected ponies (p < 0.0001).

Bottom Line: Infection with either virus led to cytokine responses that coincided with the course of clinical disease, particularly the biphasic pyrexia, which correlates with respiratory disease and viremia, respectively.The ΔORF1/ORF2 virus caused significantly shorter primary pyrexia and significantly reduced nasal shedding, and an attenuated decrease in PBMC IL-8 as well as increased Tbet responses compared to WT-infected ponies.In conclusion, our findings are (i) that infection of ponies with EHV-1 leads to modulation of immune responses, which are correlated with disease pathogenesis, and (ii) that the ORF1/2 genes are of importance for disease outcome and modulation of cytokine responses.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, 300 W, Drake Rd, Fort Collins, Colorado 80523, USA. husseygs@colostate.edu.

ABSTRACT
Equine herpesvirus-1 (EHV-1) infection remains a significant problem despite the widespread use of vaccines. The inability to generate a protective immune response to EHV-1 vaccination or infection is thought to be due to immunomodulatory properties of the virus, and the ORF1 and ORF2 gene products have been hypothesized as potential candidates with immunoregulatory properties. A pony infection study was performed to define immune responses to EHV-1, and to determine if an EHV-1 ORF1/2 deletion mutant (ΔORF1/2) would have different disease and immunoregulatory effects compared to wild type EHV-1 (WT). Infection with either virus led to cytokine responses that coincided with the course of clinical disease, particularly the biphasic pyrexia, which correlates with respiratory disease and viremia, respectively. Similarly, both viruses caused suppression of proliferative T-cell responses on day 7 post infection (pi). The ΔORF1/ORF2 virus caused significantly shorter primary pyrexia and significantly reduced nasal shedding, and an attenuated decrease in PBMC IL-8 as well as increased Tbet responses compared to WT-infected ponies. In conclusion, our findings are (i) that infection of ponies with EHV-1 leads to modulation of immune responses, which are correlated with disease pathogenesis, and (ii) that the ORF1/2 genes are of importance for disease outcome and modulation of cytokine responses.

Show MeSH
Related in: MedlinePlus