RGD Reference Report - Regulatory T cells enhance persistence of the zoonotic pathogen Seoul virus in its reservoir host. - Rat Genome Database

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Regulatory T cells enhance persistence of the zoonotic pathogen Seoul virus in its reservoir host.

Authors: Easterbrook, JD  Zink, MC  Klein, SL 
Citation: Easterbrook JD, etal., Proc Natl Acad Sci U S A. 2007 Sep 25;104(39):15502-7. Epub 2007 Sep 18.
RGD ID: 2325989
Pubmed: (View Article at PubMed) PMID:17878294
DOI: Full-text: DOI:10.1073/pnas.0707453104

Hantaviruses are zoonotic pathogens that maintain a persistent infection in their reservoir hosts, yet the mechanisms mediating persistence remain unknown. Regulatory T cell responses cause persistent infection by suppressing proinflammatory and effector T cell activity; hantaviruses may exploit these responses to cause persistence. To test this hypothesis, male Norway rats were inoculated with Seoul virus and regulatory T cells were monitored during infection. Increased numbers of CD4(+)CD25(+)Forkhead box P3(+) T cells and expression of Forkhead box P3 and TGF-beta were observed in the lungs of male rats during persistent Seoul virus infection. To determine whether regulatory T cells modulate Seoul virus persistence, regulatory T cells were inactivated in male rats by using an anti-rat CD25 monoclonal antibody (NDS-63). Inactivation of regulatory T cells reduced the amount of Seoul virus RNA present in the lungs and the proportion of animals shedding viral RNA in saliva. Because regulatory T cells suppress proinflammatory-induced pathogenesis, pathologic observations in the lungs were evaluated during infection. Subclinical acute multifocal areas of hemorrhage and edema were noted in the lungs during infection; inactivation of regulatory T cells reduced the amount of pathologic foci. Expression of TNF was suppressed during the persistent phase of infection; inactivation of regulatory T cells eliminated the suppression of TNF. Taken together, these data suggest that regulatory T cells mediate Seoul virus persistence, possibly through elevated transcription and synthesis of TGF-beta and suppression of TNF. These data provide evidence of regulatory T cell involvement in the persistence of a zoonotic pathogen in its natural reservoir host.

Annotation

Disease Annotations    
Korean hemorrhagic fever  (IEP,IMP,ISO)

Gene Ontology Annotations    

Biological Process

Objects Annotated

Genes (Rattus norvegicus)
Foxp3  (forkhead box P3)
Il2ra  (interleukin 2 receptor subunit alpha)

Genes (Mus musculus)
Foxp3  (forkhead box P3)
Il2ra  (interleukin 2 receptor, alpha chain)

Genes (Homo sapiens)
FOXP3  (forkhead box P3)
IL2RA  (interleukin 2 receptor subunit alpha)


Additional Information