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Fatal disseminated mouse adenovirus type 1 infection in mice lacking B cells or Bruton's tyrosine kinase.

Abstract
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.
AuthorsMartin L Moore, Erin L McKissic, Corrie C Brown, John E Wilkinson, Katherine R Spindler
JournalJournal of virology (J Virol) Vol. 78 Issue 11 Pg. 5584-90 (Jun 2004) ISSN: 0022-538X [Print] United States
PMID15140955 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • FASLG protein, human
  • Fas Ligand Protein
  • Fasl protein, mouse
  • Membrane Glycoproteins
  • RNA, Messenger
  • Protein-Tyrosine Kinases
  • Agammaglobulinaemia Tyrosine Kinase
  • BTK protein, human
  • Btk protein, mouse
Topics
  • Adenoviridae Infections (immunology)
  • Agammaglobulinaemia Tyrosine Kinase
  • Animals
  • B-Lymphocytes (physiology)
  • Disease Susceptibility
  • Encephalomyelitis (etiology)
  • Enteritis (etiology)
  • Fas Ligand Protein
  • Immunization, Passive
  • Membrane Glycoproteins (genetics)
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Protein-Tyrosine Kinases (physiology)
  • RNA, Messenger (analysis)
  • Viral Load

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