TY - JOUR
T1 - Alteration of clinical outcome and histopathology of yellow fever virus infection in a hamster model by previous infection with heterologous flaviviruses
AU - Xiao, Shu Yuan
AU - Guzman, Hilda
AU - Travassos Da Rosa, Amelia P.A.
AU - Zhu, Hong Bing
AU - Tesh, Robert B.
PY - 2003/6
Y1 - 2003/6
N2 - Using a recently described hamster model of severe yellow fever (YF), we examined the hypothesis that prior infection with heterologous flaviviruses protects against severe or fatal YF. Hamsters were singly or sequentially infected with Japanese encephalitis, St. Louis encephalitis, West Nile, and/or dengue-1 viruses, and then challenged with a virulent strain of yellow fever virus (YFV). In contrast to control (naive) hamsters, many of which appeared clinically ill or died after YFV infection, the flavivirus-immune animals remained asymptomatic. The flavivirus-immune hamsters also had a reduced viremia and lower serum levels of alanine aminotransferase and total bilirubin, compared with naive hamsters, following YFV infection. Histologically, livers of animals in the flavivirus-immune and control groups showed comparable levels of multifocal necrapoptosis. However, steatosis was not observed in the flavivirus-immune animals, whereas naive hamsters developed extensive microvesicular steatosis in the liver following YFV infection. These findings suggest that hepatocytic steatosis is an adverse microscopic feature associated with severe disease in YFV infection. Our experimental results support earlier anecdotal reports that prior exposure of humans to heterologous flaviviruses reduces subsequent risk of fatal YFV infection.
AB - Using a recently described hamster model of severe yellow fever (YF), we examined the hypothesis that prior infection with heterologous flaviviruses protects against severe or fatal YF. Hamsters were singly or sequentially infected with Japanese encephalitis, St. Louis encephalitis, West Nile, and/or dengue-1 viruses, and then challenged with a virulent strain of yellow fever virus (YFV). In contrast to control (naive) hamsters, many of which appeared clinically ill or died after YFV infection, the flavivirus-immune animals remained asymptomatic. The flavivirus-immune hamsters also had a reduced viremia and lower serum levels of alanine aminotransferase and total bilirubin, compared with naive hamsters, following YFV infection. Histologically, livers of animals in the flavivirus-immune and control groups showed comparable levels of multifocal necrapoptosis. However, steatosis was not observed in the flavivirus-immune animals, whereas naive hamsters developed extensive microvesicular steatosis in the liver following YFV infection. These findings suggest that hepatocytic steatosis is an adverse microscopic feature associated with severe disease in YFV infection. Our experimental results support earlier anecdotal reports that prior exposure of humans to heterologous flaviviruses reduces subsequent risk of fatal YFV infection.
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U2 - 10.4269/ajtmh.2003.68.695
DO - 10.4269/ajtmh.2003.68.695
M3 - Article
C2 - 12887029
AN - SCOPUS:0043239102
SN - 0002-9637
VL - 68
SP - 695
EP - 703
JO - American Journal of Tropical Medicine and Hygiene
JF - American Journal of Tropical Medicine and Hygiene
IS - 6
ER -