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J Virol, August 1998, p. 6884-6887, Vol. 72, No. 8
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Increased Susceptibility of Diabetic Mice to Influenza Virus Infection: Compromise of Collectin-Mediated Host Defense of the Lung by Glucose?

Patrick C. Reading,1 Janette Allison,2 Erika C. Crouch,3 and E. Margot Anders1,*

Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria 3052,1 and The Walter and Eliza Hall Institute of Medical Research, P.O. Royal Melbourne Hospital, Victoria 3052,2 Australia, and Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 631103

Received 18 March 1998/Accepted 24 April 1998

The influence of diabetes on susceptibility to influenza virus infection was examined in a mouse model in which RIP-Kb transgenic mice and their nontransgenic littermates were used as the diabetic and nondiabetic hosts, respectively. Influenza virus A/Phil/82 (H3N2) grew to significantly higher titers in the lungs of diabetic than nondiabetic mice. The extent of viral replication in the lungs was proportional to blood glucose levels in the mice at the time of infection, and the enhanced susceptibility of diabetic mice was reversed with insulin. Growth of A/HKx31 (H3N2) virus was also enhanced in diabetic mice, whereas the highly virulent strain A/PR/8/34 (H1N1) showed no difference in virus yields in diabetic and nondiabetic mice, even with low inocula. A/Phil/82 and A/HKx31 are sensitive to neutralization in vitro by the pulmonary collectin surfactant protein D (SP-D), whereas A/PR/8/34 is essentially resistant. Glucose is a ligand for SP-D, and neutralization of A/Phil/82 virus by SP-D was abolished in the presence of glucose at levels commonly found in diabetic mice. These findings suggest that in mice, and perhaps in humans, diabetes predisposes to influenza virus infection through compromise of collectin-mediated host defense of the lung by glucose.


* Corresponding author. Mailing address: Dept. of Microbiology and Immunology, University of Melbourne, Grattan St., Parkville, Victoria 3052, Australia. Phone: 61 3 9344 5702. Fax: 61 3 9347 1540. E-mail: m.anders{at}microbiology.unimelb.edu.au.


J Virol, August 1998, p. 6884-6887, Vol. 72, No. 8
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.



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