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Journal of Virology, June 2004, p. 5584-5590, Vol. 78, No. 11
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.11.5584-5590.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Fatal Disseminated Mouse Adenovirus Type 1 Infection in Mice Lacking B Cells or Bruton's Tyrosine Kinase

Martin L. Moore,1,{dagger} Erin L. McKissic,2 Corrie C. Brown,3 John E. Wilkinson,4 and Katherine R. Spindler5*

Department of Genetics, Franklin College of Arts and Sciences,1 Department of Pathology, College of Veterinary Medicine, University of Georgia, Athens, Georgia 30602,3 Department of Epidemiology, University of Michigan School of Public Health,2 and Department of Pathology and Unit for Lab Animal Medicine,4 Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan 481095

Received 8 October 2003/ Accepted 26 January 2004

Mouse adenovirus type 1 (MAV-1) infection of B-cell-deficient and Bruton's tyrosine kinase (Btk)-deficient mice resulted in fatal disseminated disease resembling human adenovirus infections in immunocompromised patients. Mice lacking B cells or Btk were highly susceptible to acute MAV-1 infection, in contrast to controls and mice lacking T cells. To our knowledge, this is the first demonstration that mice with an X-linked immunodeficiency phenotype (Btk deficient) are susceptible to virus-induced disease. Mice lacking B cells or Btk on a C57BL/6 background succumbed with encephalomyelitis, hepatitis, and lymphoid necrosis. Mice lacking B cells on a BALB/c background succumbed with enteritis and hepatitis. Survival of acute MAV-1 infection correlated with early T-cell-independent neutralizing antibody and T-cell-independent antiviral immunoglobulin M. Treatment of MAV-1-infected Btk–/– mice 4 to 9 days postinfection with antiserum harvested 6 to 9 days postinfection from MAV-1-infected Btk+/+ mice was therapeutic. Our findings implicate a critical role for B-cell function in preventing disseminated MAV-1 infection, particularly production of early T-cell-independent antiviral immunoglobulin M.

* Corresponding author. Mailing address: University of Michigan Medical School, 1150 W. Medical Center Dr., 6724 Medical Science Bldg. II, Ann Arbor, MI 48109-0620. Phone: (734) 615-2727. Fax: (734) 764-3562. E-mail: krspin{at}umich.edu.

{dagger} Present address: Department of Medicine, Vanderbilt University Medical Center, Nashville, Tenn.

Journal of Virology, June 2004, p. 5584-5590, Vol. 78, No. 11
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.11.5584-5590.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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