Specific history of heterologous virus infections determines anti-viral immunity and immunopathology in the lung

UMMS Affiliation

Department of Pathology

Publication Date


Document Type



Animals; Cell Line; Cercopithecus aethiops; Cytokines; Genes, Viral; *Immunity; Lung; Lymphocytes; Macrophages; Male; Mice; Mice, Inbred C57BL; Orthomyxoviridae Infections; Respiratory Tract Infections; Vaccinia; Vero Cells; Virus Diseases; Viruses


Life Sciences | Medicine and Health Sciences


Having previously shown that previous immunity to one virus can influence the host response to a subsequent unrelated virus, we questioned whether the outcome to a given virus infection would be altered in similar or different ways by previous immunity to different viruses, and whether immunity to a given virus would have similar effects on all subsequent infections. In mouse models of respiratory viral infections, immunity to lymphocytic choriomeningitis virus (LCMV), murine cytomegalovirus (MCMV), or influenza A virus enhanced both Th1-type cytokine responses and viral clearance in the lung on vaccinia virus infection. A common pathological feature was the presence of chronic mononuclear infiltrates instead of the acute polymorphonuclear response seen in the infected nonimmune mice, but some pathologies such as enhanced bronchus-associated lymphoid tissue and bronchiolitis obliterans were unique for the immunizing virus, LCMV. Immunity to influenza virus influenced subsequent infections diversely, inhibiting vaccinia virus but enhancing LCMV and MCMV titers and completely altering cytokine profiles. Influenza virus immunity enhanced the mild mononuclear responses usually observed during acute infections with MCMV or LCMV in nonimmune mice, but unique features such as enhanced bronchiolization and mononuclear consolidation occurred during MCMV infection of influenza virus-immune mice. Heterologous immunity induced two patterns of disease outcome dependent on the specific virus infection sequence: improved, if the acute response switched from a neutrophilic to a lymphocytic response or worsened, if it switched from a mild to a severe lymphocytic response. Heterologous immunity thus occurs between many viruses, resulting in altered protective immunity and lung immunopathology, and this is influenced by the specific virus infection sequence.

DOI of Published Version



Am J Pathol. 2003 Oct;163(4):1341-55.

Journal/Book/Conference Title

The American journal of pathology

Related Resources

Link to article in PubMed

PubMed ID