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1 October 2000 Exposure to Ultraviolet Radiation Enhances Mortality and Pathology Associated with Influenza Virus Infection in Mice
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Ultraviolet radiation (UVR) causes systemic immune suppression, decreasing the delayed type and contact hypersensitivity responses in animals and humans and enhancing certain mycobacterial, parasitic and viral infections in mice. This study tests the hypothesis that prior exposure to UVR enhances influenza infections in mice. BALB/c female mice were exposed to 0–8.2 kJ/m2 of UVR. Exposed and unexposed mice were infected intranasally three days later with 150–300 plaque-forming units/mouse (lethal dose (LD)20–LD40) of mouse-adapted Hong Kong Influenza A/68 (H3N2) virus or sham infected with 50 μL Hanks' balanced salt solution/mouse. Mortality from viral infection ranged from 25–50%. UVR exposure increased virus-associated mortality in a dose-dependent manner (up to a two-fold increase at 8.2 kJ/m2). The increased mortality was not associated with bacterial pneumonia. The highest dose of UVR also accelerated the body weight loss and increased the severity and incidence of thymic atrophy associated with influenza infection. However, UVR treatment had little effect on the increase in lung wet weight seen with viral infection, and, to our surprise, did not cause an increase in virus titers in the lung or dissemination of virus. The mice died 5–6 days after infection, too early for adaptive immune responses to have much impact. Also, UVR did not interfere with the development of protective immunity to influenza, as measured by reinfection with a lethal challenge of virus. Also, cells adoptively transferred from UVR or untreated mice were equally protective of recipient mice challenged with a lethal dose of virus. The mice resemble mice succumbing to endotoxin, and influenza infection increased the levels of tumor necrosis factor α (TNF-α) in bronchoalveolar lavage fluid and serum cortisol levels; however, UVR preexposure did not increase either of these responses to the virus. The results show that UVR increased the morbidity, mortality and pathogenesis of influenza virus in mice without affecting protective immunity to the virus, as measured by resistance to reinfection. The mechanism of enhanced mortality is uncertain, but the data raises concerns that UVR may exacerbate early responses that contribute to the pathogenesis of a primary viral infection.

Lisa K. Ryan, Donna L. Neldon, Lisa R. Bishop, M. Ian Gilmour, Mary J. Daniels, Denise M. Sailstad, and Mary Jane K. Selgrade "Exposure to Ultraviolet Radiation Enhances Mortality and Pathology Associated with Influenza Virus Infection in Mice," Photochemistry and Photobiology 72(4), 497-507, (1 October 2000).<0497:ETUREM>2.0.CO;2
Received: 28 June 2000; Accepted: 1 July 2000; Published: 1 October 2000

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