Defective interfering influenza virus confers only short-lived protection against influenza virus disease: Evidence for a role for adaptive immunity in DI virus-mediated protection in vivo

• Published in: Vaccine Vol. 29; no. 38; pp. 6584 - 6591
• Main Authors: Scott, Paul D, Meng, Bo, Marriott, Anthony C, Easton, Andrew J, Dimmock, Nigel J
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 02.09.2011; Elsevier; Elsevier Limited; Elsevier Science
• Subjects: acute course; Adaptive Immunity; Allergy and Immunology; Animals; Applied microbiology; Atoms & subatomic particles; B-Lymphocytes - immunology; Biological and medical sciences; Cloning; Competition; Defective interfering; Defective Viruses - immunology; Disease; Fundamental and applied biological sciences. Psychology; genome; Genomes; Immune system; Immunity; Infections; Influenza; Influenza A virus; Influenza A virus - immunology; Influenza Vaccines - administration & dosage; Influenza Vaccines - immunology; Killer Cells, Natural - immunology; Lung - virology; lungs; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Mice, SCID; Microbiology; Miscellaneous; nucleotide sequences; Orthomyxoviridae; Orthomyxoviridae Infections - immunology; Orthomyxoviridae Infections - pathology; Orthomyxoviridae Infections - prevention & control; Orthomyxoviridae Infections - virology; Protection; RNA; SCID; severe combined immunodeficiency; Studies; T-lymphocytes; T-Lymphocytes - immunology; vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Viral Load; Virology; Viruses; Defective interfering; Immunity; Protection; SCID; Influenza; Orthomyxoviridae; Influenzavirus; Infection; Virus; Influenzavirus A; Influenza A virus; Viral disease; Combined immune deficiency
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2011.06.114

We have shown earlier that a single dose of cloned defective interfering (DI) influenza A virus strongly protects mice from disease following a lethal challenge with different subtypes of influenza A virus. These animals suffered no clinical disease but experienced a subclinical infection which rendered them immune to reinfection with the same challenge virus. However, little is known about how DI virus achieves such protection. Here we investigated the role of adaptive immunity in DI virus-mediated protection using severe-combined immunodeficient (SCID) mice, which lack competence in both B- and T-cell compartments but retain NK cell activity. SCID mice which were treated with DI virus and infected with influenza virus initially remained completely well, while infected litter mates that received UV-inactivated DI virus became seriously ill and died. However, after 10 days of good health, the DI virus-protected SCID mice developed a clinical disease that was similar, but not completely identical, to the acute influenza disease. Disease was delayed longer by a higher dose of DI virus. We excluded the possibilities that the DI virus load in the lungs had declined, that the DI RNA sequence had changed so that it no longer interfered with the infectious genome, or that infectious virus had become resistant to the DI virus. These data show that while DI virus provides full protection from the acute disease in the absence of adaptive immunity, that same immunity is essential for clearing the infection. This indicates that the conventional view that DI virus-induced protection is mediated solely by competition for replication with the challenge virus is incorrect for influenza virus.