Fatal disseminated mouse adenovirus type 1 infection in mice lacking B cells or Bruton's tyrosine kinase.
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.
Moore
Martin L
ML
University of Michigan Medical School, 1150 W. Medical Center Dr., 6724 Medical Science Bldg. II, Ann Arbor, MI 48109-0620, USA.
McKissic
Erin L
EL
Brown
Corrie C
CC
Wilkinson
John E
JE
Spindler
Katherine R
KR
D000257:Adenoviridae Infections / Q000276:immunology*; D000077329:Agammaglobulinaemia Tyrosine Kinase; D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D004198:Disease Susceptibility; D004679:Encephalomyelitis / Q000209:etiology; D004751:Enteritis / Q000209:etiology; D053222:Fas Ligand Protein; D007116:Immunization, Passive; D008562:Membrane Glycoproteins / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D019562:Viral Load
C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human; C000625951:Btk protein, mouse