Protection of mice from lethal influenza by defective interfering virus: T cell responses

McLain, Lesley; Morgan, David; Dimmock, Nigel J.

doi:10.1099/0022-1317-73-2-375

Cited by 14 publications

(11 citation statements)

References 28 publications

(34 reference statements)

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“…Earlier, the importance of T lymphocytes in host-dependent pathology was already reported in the context of influenza virus infection in mice (29), where depletion of CD4 ϩ and CD8 ϩ T cells before influenza inoculation prevented morbidity, in agreement with our findings. However, the interplay of these populations is still unclear; depletion of CD4 ϩ cells might result in lack of help to pathological CD8 ϩ cells.…”

Section: Discussionsupporting

confidence: 93%

Lack of CD200 Enhances Pathological T Cell Responses during Influenza Infection

Rygiel

Rijkers

Ruiter

et al. 2009

The Journal of Immunology

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Influenza virus infection can be accompanied by life-threatening immune pathology most likely due to excessive antiviral responses. Inhibitory immune receptors may restrain such overactive immune responses. To study the role of the inhibitory immune receptor CD200R and its ligand CD200 during influenza infection, we challenged wild-type and CD200−/− mice with influenza virus. We found that CD200−/− mice in comparison to wild-type controls when inoculated with influenza virus developed more severe disease, associated with increased lung infiltration and lung endothelium damage. CD200−/− mice did develop adequate adaptive immune responses and were able to control viral load, suggesting that the severe disease was caused by a lack of control of the immune response. Interestingly, development of disease was completely prevented by depletion of T cells before infection, despite dramatically increased viral load, indicating that T cells are essential for the development of disease symptoms. Our data show that lack of CD200-CD200R signaling increases immune pathology during influenza infection, which can be reduced by T cell depletion.

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Section: Discussionsupporting

confidence: 93%

Lack of CD200 Enhances Pathological T Cell Responses during Influenza Infection

Rygiel

Rijkers

Ruiter

et al. 2009

The Journal of Immunology

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“…Analysis of the specificity of T cell responses using vaccinia viruses expressing individual influenza A virus proteins showed that, unusually for influenza A virus infections, the response in A/WSN-infected, DI virus-treated mice was largely strain specific. Depletion of both CD8 + and CD4 + cells with specific antibody was needed to abolish lung consolidation and for mice infected with A/WSN or A/WSN + inactivated DI virus to survive [19], but like the SCID mice reported here, infectious virus in the lung was not cleared. In contrast, when mice depleted of CD8 + and CD4 + cells were inoculated with A/WSN + DI virus, lung infectivity was cleared, presumably with the assistance of local, T cell-independent, virus-specific antibody.…”

Section: Discussionmentioning

confidence: 77%

“…These mice all died. CTL responses were diminished in mice inoculated with A/WSN + DI virus and these all survived [19]. Analysis of the specificity of T cell responses using vaccinia viruses expressing individual influenza A virus proteins showed that, unusually for influenza A virus infections, the response in A/WSN-infected, DI virus-treated mice was largely strain specific.…”

Section: Discussionmentioning

confidence: 99%

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

Scott

Meng

Marriott

et al. 2011

Vaccine

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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.

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“…In fact, this is in line with the almost universal reassortment of full-length RNAs which takes place between influenza A strains, for which a requirement for mutual replication and encapsidation is mandatory. Nonetheless, this interaction is not universal as DI WSN did not protect mice against PR8 (McLain et al, 1992;unpublished data).…”

Section: Discussionmentioning

confidence: 98%