Host factors influencing viral persistence
Research output: Contribution to journal › Journal article › Research › peer-review
With the aim of characterizing the antiviral immune response to a non-cytocidal virus, we studied the outcome of lymphocytic choriomeningitis virus infection in a number of gene knockout mouse strains. Two virus strains differing markedly in their capacity to spread and replicate inside the murine host were used. Our results reveal that very different outcomes may be observed depending on virus strain and immunocompetence of the host. Thus while CD4+ cells are not critical during the initial phase of virus control, infectious virus reappear in mice lacking CD4+ cells, B cells or CD40 ligand. Reappearance of virus is associated with impaired long-term CD8+ T-cell mediated immune surveillance, and the time to virus resurgence is inversely correlated to the replication rate of the virus. Our studies also reveal that interferon-gamma is a central cytokine, and depending on the rate of virus replication, mice lacking the ability to produce interferon-gamma may develop either a severe, mostly fatal, T-cell mediated wasting syndrome or a chronic infection characterized by long-term coexistence of antiviral cytotoxic T lymphocytes and infectious virus. Mathematical modelling indicates that these different outcomes may be explained in relatively simple mathematical terms. This suggests that modelling may be used as a means to predict critical host and virus parameters. Therefore, combining mathematical modelling with precise, quantitative, in vivo analyses looks to be a promising approach in addressing central quantitative issues in immunobiology.
Original language | English |
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Journal | Philosophical Transactions of the Royal Society of London. Biological Sciences |
Volume | 355 |
Issue number | 1400 |
Pages (from-to) | 1031-41 |
Number of pages | 10 |
ISSN | 0962-8436 |
DOIs | |
Publication status | Published - 2000 |
Bibliographical note
Keywords: Animals; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Immunologic Memory; Lymphocytic Choriomeningitis; Lymphocytic choriomeningitis virus; Mice
ID: 9639470