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Epstein-Barr virus IL-10 gene expression by a recombinant murine gammaherpesvirus in vivo enhances acute pathogenicity but does not affect latency or reactivation.

Lindquester GJ, Greer KA, Stewart JP, Sample JT - Herpesviridae (2014)

Bottom Line: Many viral genes affect cytokine function within infected hosts, with interleukin 10 (IL-10) as a commonly targeted mediator.Recombinant murine gammaherpesvirus expressing EBV vIL-10 rose to significantly higher titers in lungs and promoted an increase in spleen cell number in infected mice in comparison to MHV strains lacking the vIL-10 gene.Given that EBV and MHV wild-type strains contain other genes that induce cIL-10 expression in latency (e.g. LMP-1 and M2, respectively), vIL-10 may have evolved to serve the specific role in acute infection of enlarging the permissive host cell population, perhaps to facilitate initial survival and dissemination of viral-infected cells.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biology, Rhodes College, Memphis, TN 38112, USA.

ABSTRACT

Background: Many viral genes affect cytokine function within infected hosts, with interleukin 10 (IL-10) as a commonly targeted mediator. Epstein-Barr virus (EBV) encodes an IL-10 homologue (vIL-10) expressed during productive (lytic) infection and induces expression of cellular IL-10 (cIL-10) during latency. This study explored the role of vIL-10 in a murine gammaherpesvirus (MHV) model of viral infection.

Methods: The EBV vIL-10 gene was inserted into MHV-76, a strain which lacks the ability to induce cIL-10, by recombination in transfected mouse cells. Mice were infected intranasally with the recombinant, vIL-10-containing MHV-76 or control virus strains and assayed at various days post infection for lung virus titer, spleen cell number, percentage of latently infected spleen cells and ability to reactivate virus from spleen cells.

Results: Recombinant murine gammaherpesvirus expressing EBV vIL-10 rose to significantly higher titers in lungs and promoted an increase in spleen cell number in infected mice in comparison to MHV strains lacking the vIL-10 gene. However, vIL-10 expression did not alter the quantity of latent virus in the spleen or its ability to reactivate.

Conclusions: In this mouse model of gammaherpesvirus infection, EBV vIL-10 appears to influence acute-phase pathogenicity. Given that EBV and MHV wild-type strains contain other genes that induce cIL-10 expression in latency (e.g. LMP-1 and M2, respectively), vIL-10 may have evolved to serve the specific role in acute infection of enlarging the permissive host cell population, perhaps to facilitate initial survival and dissemination of viral-infected cells.

No MeSH data available.


Related in: MedlinePlus

vIL10 does not affect the quantity of latent virus. Spleen cells underwent three-fold dilutions with 12 duplicate wells per dilution. Viral DNA was detected by nested PCR to orf50. Curve-fit lines represent results of nonlinear regression analysis. Data points represent the mean of two independent experiments with spleens pooled from five mice per experiment. Results indicate no difference between MHV-76 and recombinants with or without vIL10.
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Figure 6: vIL10 does not affect the quantity of latent virus. Spleen cells underwent three-fold dilutions with 12 duplicate wells per dilution. Viral DNA was detected by nested PCR to orf50. Curve-fit lines represent results of nonlinear regression analysis. Data points represent the mean of two independent experiments with spleens pooled from five mice per experiment. Results indicate no difference between MHV-76 and recombinants with or without vIL10.

Mentions: The presence of viral genomes in splenocytes early in latency was assayed by limiting-dilution PCR. Previous studies have shown a defect in latency for MHV-76 as compared to MHV-68 following i.n. inoculation[44,45]. While Figure 6 does not exhibit a significant difference in PCR-positive cells for the sample size and dilutions tested, MHV-68 trends toward a higher number of positive cells, and MHV-76 and 76.vIL10 track together. Importantly, the expected differences in reactivation between MHV-68 and MHV-76[44,45] are observed in Figure 7. Data indicate no significant difference in reactivation of MHV-76 with or without vIL-10.


Epstein-Barr virus IL-10 gene expression by a recombinant murine gammaherpesvirus in vivo enhances acute pathogenicity but does not affect latency or reactivation.

Lindquester GJ, Greer KA, Stewart JP, Sample JT - Herpesviridae (2014)

vIL10 does not affect the quantity of latent virus. Spleen cells underwent three-fold dilutions with 12 duplicate wells per dilution. Viral DNA was detected by nested PCR to orf50. Curve-fit lines represent results of nonlinear regression analysis. Data points represent the mean of two independent experiments with spleens pooled from five mice per experiment. Results indicate no difference between MHV-76 and recombinants with or without vIL10.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4199788&req=5

Figure 6: vIL10 does not affect the quantity of latent virus. Spleen cells underwent three-fold dilutions with 12 duplicate wells per dilution. Viral DNA was detected by nested PCR to orf50. Curve-fit lines represent results of nonlinear regression analysis. Data points represent the mean of two independent experiments with spleens pooled from five mice per experiment. Results indicate no difference between MHV-76 and recombinants with or without vIL10.
Mentions: The presence of viral genomes in splenocytes early in latency was assayed by limiting-dilution PCR. Previous studies have shown a defect in latency for MHV-76 as compared to MHV-68 following i.n. inoculation[44,45]. While Figure 6 does not exhibit a significant difference in PCR-positive cells for the sample size and dilutions tested, MHV-68 trends toward a higher number of positive cells, and MHV-76 and 76.vIL10 track together. Importantly, the expected differences in reactivation between MHV-68 and MHV-76[44,45] are observed in Figure 7. Data indicate no significant difference in reactivation of MHV-76 with or without vIL-10.

Bottom Line: Many viral genes affect cytokine function within infected hosts, with interleukin 10 (IL-10) as a commonly targeted mediator.Recombinant murine gammaherpesvirus expressing EBV vIL-10 rose to significantly higher titers in lungs and promoted an increase in spleen cell number in infected mice in comparison to MHV strains lacking the vIL-10 gene.Given that EBV and MHV wild-type strains contain other genes that induce cIL-10 expression in latency (e.g. LMP-1 and M2, respectively), vIL-10 may have evolved to serve the specific role in acute infection of enlarging the permissive host cell population, perhaps to facilitate initial survival and dissemination of viral-infected cells.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biology, Rhodes College, Memphis, TN 38112, USA.

ABSTRACT

Background: Many viral genes affect cytokine function within infected hosts, with interleukin 10 (IL-10) as a commonly targeted mediator. Epstein-Barr virus (EBV) encodes an IL-10 homologue (vIL-10) expressed during productive (lytic) infection and induces expression of cellular IL-10 (cIL-10) during latency. This study explored the role of vIL-10 in a murine gammaherpesvirus (MHV) model of viral infection.

Methods: The EBV vIL-10 gene was inserted into MHV-76, a strain which lacks the ability to induce cIL-10, by recombination in transfected mouse cells. Mice were infected intranasally with the recombinant, vIL-10-containing MHV-76 or control virus strains and assayed at various days post infection for lung virus titer, spleen cell number, percentage of latently infected spleen cells and ability to reactivate virus from spleen cells.

Results: Recombinant murine gammaherpesvirus expressing EBV vIL-10 rose to significantly higher titers in lungs and promoted an increase in spleen cell number in infected mice in comparison to MHV strains lacking the vIL-10 gene. However, vIL-10 expression did not alter the quantity of latent virus in the spleen or its ability to reactivate.

Conclusions: In this mouse model of gammaherpesvirus infection, EBV vIL-10 appears to influence acute-phase pathogenicity. Given that EBV and MHV wild-type strains contain other genes that induce cIL-10 expression in latency (e.g. LMP-1 and M2, respectively), vIL-10 may have evolved to serve the specific role in acute infection of enlarging the permissive host cell population, perhaps to facilitate initial survival and dissemination of viral-infected cells.

No MeSH data available.


Related in: MedlinePlus