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Int J Clin Exp Pathol 1(2):169-179;2008

Original Article
Yellow Fever Virus Infection in Syrian Golden Hamsters: Relationship between Cytokine
Expression and Pathologic Changes

Guangyu Li, Tao Duan, Xiaoyan Wu, Robert B. Tesh, Lynn Soong and Shu-Yuan Xiao

Department of Pathology, and Center for Biodefense and Emerging Infectious Diseases, Institute for Human Infections and Immunity;
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA; Department of Medicine, Zhong
Nan Hospital, Wuhan University, Wuhan, Hubei Province, China

Received 1 Aug 2007; accepted and available online 1 January 2008

Abstract: Infection of primates by yellow fever virus (YFV) often results in severe multi-organ failure with marked histologic abnormalities.
However, the role of host’s immune response, particularly innate immunity, in disease process is unclear. In this study, we used a well
established hamster model of yellow fever to examine the dynamic changes of cytokine expression and histopathology in the liver, spleen,
kidney, and heart during the course of YFV infection. We observed that the levels of inflammatory cytokines (IFN-γ, IL-2, TNF-α) in the liver were
significantly reduced in the mid-stage of infection (8 days), but were elevated later (12 days). In contrast, IL-12p40 was elevated throughout the
infection. The levels of IFN-γ, IL-2, and TNF-α were increased in the spleen, kidney, and heart throughout the study period. For regulatory
cytokines, IL-10 was significantly increased, and TGF-β was reduced in the liver, spleen and heart in both early and mid-stages of infection, but
was elevated in the kidney during the entire course of infection. In view of the pathologic changes, the observed cytokine profiles suggest that
YFV has immunosuppressive effects, which contribute to liver damage in the mid-stage of infection, followed by an immunopathogenic
mechanism that leads to disease progression during the late-stages of infection. Our findings support the hypothesis that organ injury by YFV
is probably due to a combination of multiple factors, including direct viral injury and host innate immune responses.(IJCEP708001).

Key Words: Yellow fever virus, pathogenesis, cytokines, RT-PCR, pathology, immunohistochemistry

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Address all correspondence to: Shu-Yuan Xiao, M.D., Department of Pathology, University of Texas Medical Branch, 301 University Boulevard,
Galveston, TX 77555-0588; Email:
syxiao@utmb.edu; Tel: 409-772-8447; Fax: 409-747-2429.