Abstract
Human cytomegalovirus (HCMV) and many other pathogens exploit the IL-10 pathway, as part of their infectious cycle, either through their own encoded IL-10 (hcmvIL-10 for HCMV) or manipulation of the cellular IL-10 signaling cascade. Based on the in vitro demonstrations of its pleiotropic and cell type-dependent modulatory nature, hcmvIL-10 could profoundly attenuate host immunity, facilitating the establishment and maintenance of a persistent infection in an immune-competent host. To investigate the impact of extrinsic IL-10 on the induction and maintenance of antiviral immune responses in vivo, rhesus macaques were inoculated with variants of rhesus cytomegalovirus (RhCMV) either expressing or lacking the RhCMV ortholog of hcmvIL-10 (rhcmvIL-10). The results show that rhcmvIL-10 alters the earliest host responses to viral antigens by dampening the magnitude and specificity of innate effector cells to primary RhCMV infection. In addition, there is a commensurate reduction in the quality and quantity of early and long-term, RhCMV-specific adaptive immune responses. These findings provide a mechanistic basis of how early interactions between a newly infected host and HCMV could shape the long-term virus-host balance, which may facilitate the development of new prevention and intervention strategies for HCMV.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 22647-22652 |
| Number of pages | 6 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 107 |
| Issue number | 52 |
| DOIs | |
| State | Published - Dec 28 2010 |
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Keywords
- Immune evasion
- Monkey model
ASJC Scopus subject areas
- General
Cite this
Attenuation of innate immunity by cytomegalovirus IL-10 establishes a long-term deficit of adaptive antiviral immunity. / Chang, W. L William; Barry, Peter A.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 107, No. 52, 28.12.2010, p. 22647-22652.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Attenuation of innate immunity by cytomegalovirus IL-10 establishes a long-term deficit of adaptive antiviral immunity
AU - Chang, W. L William
AU - Barry, Peter A
PY - 2010/12/28
Y1 - 2010/12/28
N2 - Human cytomegalovirus (HCMV) and many other pathogens exploit the IL-10 pathway, as part of their infectious cycle, either through their own encoded IL-10 (hcmvIL-10 for HCMV) or manipulation of the cellular IL-10 signaling cascade. Based on the in vitro demonstrations of its pleiotropic and cell type-dependent modulatory nature, hcmvIL-10 could profoundly attenuate host immunity, facilitating the establishment and maintenance of a persistent infection in an immune-competent host. To investigate the impact of extrinsic IL-10 on the induction and maintenance of antiviral immune responses in vivo, rhesus macaques were inoculated with variants of rhesus cytomegalovirus (RhCMV) either expressing or lacking the RhCMV ortholog of hcmvIL-10 (rhcmvIL-10). The results show that rhcmvIL-10 alters the earliest host responses to viral antigens by dampening the magnitude and specificity of innate effector cells to primary RhCMV infection. In addition, there is a commensurate reduction in the quality and quantity of early and long-term, RhCMV-specific adaptive immune responses. These findings provide a mechanistic basis of how early interactions between a newly infected host and HCMV could shape the long-term virus-host balance, which may facilitate the development of new prevention and intervention strategies for HCMV.
AB - Human cytomegalovirus (HCMV) and many other pathogens exploit the IL-10 pathway, as part of their infectious cycle, either through their own encoded IL-10 (hcmvIL-10 for HCMV) or manipulation of the cellular IL-10 signaling cascade. Based on the in vitro demonstrations of its pleiotropic and cell type-dependent modulatory nature, hcmvIL-10 could profoundly attenuate host immunity, facilitating the establishment and maintenance of a persistent infection in an immune-competent host. To investigate the impact of extrinsic IL-10 on the induction and maintenance of antiviral immune responses in vivo, rhesus macaques were inoculated with variants of rhesus cytomegalovirus (RhCMV) either expressing or lacking the RhCMV ortholog of hcmvIL-10 (rhcmvIL-10). The results show that rhcmvIL-10 alters the earliest host responses to viral antigens by dampening the magnitude and specificity of innate effector cells to primary RhCMV infection. In addition, there is a commensurate reduction in the quality and quantity of early and long-term, RhCMV-specific adaptive immune responses. These findings provide a mechanistic basis of how early interactions between a newly infected host and HCMV could shape the long-term virus-host balance, which may facilitate the development of new prevention and intervention strategies for HCMV.
KW - Immune evasion
KW - Monkey model
UR - http://www.scopus.com/inward/record.url?scp=78651102604&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=78651102604&partnerID=8YFLogxK
U2 - 10.1073/pnas.1013794108
DO - 10.1073/pnas.1013794108
M3 - Article
C2 - 21149711
AN - SCOPUS:78651102604
VL - 107
SP - 22647
EP - 22652
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 52
ER -